Clinical Trials Register

Summary
EudraCT Number:	2011-004094-93
Sponsor's Protocol Code Number:	PAFCUTIII
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:	2012-02-21
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

2011-004094-93

A.3

Full title of the trial

Double-blind, three-way cross-over, placebo controlled study to assess the efficacy, safety and mechanisms of treatment with rupatadine 20 and 40 mg in cold contact urticaria (CCU)

Función de la liberación de la Histamina y del factor de activación plaquetario (PAF) en la inflamación cutánea después de la provocación con agua fría en pacientes con urticaria por contacto al frío (CCU) tratados con rupatadina 20 y 40 mg. Estudio aleatorizado, doble ciego, cruzado de tres vías y controlado por placebo

A.3.1

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

Double-blind, three-way cross-over, placebo controlled study to assess the efficacy, safety and mechanisms of treatment with rupatadine 20 and 40 mg in cold contact urticaria (CCU)

A.3.2

Name or abbreviated title of the trial where available

PAFCUTIII

A.4.1

Sponsor's protocol code number

PAFCUTIII

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	Consorci Mar Parc de Salut de Barcelona
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	J. Uriach y Compañía, 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	Consorci Mar Parc de Salut de Barcelona
B.5.2	Functional name of contact point	Ana Gimenez-Arnau
B.5.3	Address:
B.5.3.1	Street Address	Dr. Aiguader, 88
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08003
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034933160678
B.5.5	Fax number	0034934144909
B.5.6	E-mail	22505aga@comb.es
B.Sponsor: 2
B.1.1	Name of Sponsor	Department of Dermatology and Allergy Charité- Universitätsmedizin Berlin
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	J. Uriach y Compañía 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	Department of Dermatology and Allergy Charité- Universitätsmedizin Berlin
B.5.2	Functional name of contact point	Department of Dermatology and Aller
B.5.3	Address:
B.5.3.1	Street Address	Charitéplatz, 1
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	D-10117
B.5.3.4	Country	Germany
B.5.4	Telephone number	004930450 51 80 43
B.5.5	Fax number	004930450 51 89 72
B.5.6	E-mail	Marcus.Maurer@charite.de

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	Rupafin 10mg
D.2.1.1.2	Name of the Marketing Authorisation holder	J. Uriach y Compañia, 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.3.1	Product name	rupatadina 10 mg
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.3.9.1	CAS number	182349-12-8
D.3.9.2	Current sponsor code	Rupatadina
D.3.9.3	Other descriptive name	RUPATADINE FUMARATE
D.3.9.4	EV Substance Code	SUB22090
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	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

Cold contact urticaria

Urticaria por contacto al frío

E.1.1.1

Medical condition in easily understood language

Cold contact urticaria

Urticaria por contacto al frío

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

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 assess the effects of rupatadine 20 mg and 40 mg on symptom development during the induction of skin lesions in CCU patients challenged with defined temperatures

Evaluar los efectos de rupatadina 20 mg y 40 mg sobre el desarrollo de los síntomas durante la inducción de lesiones cutáneas en pacientes CCU tras provocación con temperaturas definidas

E.2.2

Secondary objectives of the trial

To assess the effects of rupatadine on mast cell mediator release in blood during the induction of skin lesions in CCU patients challenged with cold water bath provocation with defined temperatures. Mediator measurements will include histamine and other mast cell-derived inflammation markers (e.g. PAF/LysoPAF, PGD2)
To assess the effect of rupatadine on mast cell activation in the skin of CCU patients
To assess the safety and tolerability of rupatadine

Evaluar los efectos de rupatadina sobre la liberación del mediador de mastocitos en sangre durante la inducción de lesiones cutáneas en pacientes CCU, tras provocación con baño de agua fría a temperaturas definidas. Las mediciones del mediador incluirán histamina y otros mastocitos derivados de marcadores de inflamación (p.ej. PAF/ LysoPAF, PGD2).
Evaluar el efecto de rupatadina sobre los mastocitos en la activación de éstos sobre la piel de los pacientes CCU.
Evaluar seguridad y tolerabilidad de rupatadina

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

?Informed consent signed and dated
?Reliable method of contraception for women of childbearing potential during the study and 3 months thereafter. A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner
?Outpatients with CCU for more than 6 weeks. confirmed by positive response with wheal and itch on Temptest®
?Age 18 and above years.
?No participation in other clinical trials 1 month before and after participation in this study

?Consentimiento Informado firmado y fechado
?Método de contracepción fiable para mujeres en edad fértil durante el ensayo y en los 3 meses posteriores. Se definen como métodos altamente efectivos de control de la natalidad aquellos que tienen una baja tasa de fallos (p.ej. menos de 1% por año) al ser usado de forma continuada y correcta, tales como implantes, inyectables, contraceptivos orales combinados, algunos DIUs, abstinencia sexual o presencia de una pareja masculina vasectomizada.
?Pacientes con CCU durante más de 6 semanas, confirmados tras respuesta positiva con pápulas y picazón por Temptest®
?Edad mayor o igual a 18 años.
?No haber participado en otros ensayos clínicos en el mes anterior a la participación en este.

E.4

Principal exclusion criteria

?Subjects who are inmates of psychiatric wards, prisons, or other state institutions. Existing or planned placement in an institution after ruling according to § 40 passage 1, number 4 AMG (Arzneimittelgesetz).
?The presence of permanent severe diseases, especially those affecting the immune system, except urticaria and cold urticaria
?The presence of permanent gastrointestinal condition which may influence the oral therapy (chronic diarrhoea diseases, congenital malformations or surgical mutilations of gastrointestinal tract)
?History or presence of epilepsy, significant neurological disorders, cerebrovascular attacks or ischemia
?History or presence of myocardial infarction or cardiac arrhythmia which requires drug therapy
?ECG alterations of repolarisation (QTc prolongations > 450ms)
?Blood pressure >180/100 mmHg and/or heart rate >100/min.
?Evidence of significant hepatic or renal disease (GOT and/or GPT 3 times above the upper reference value, serum creatinine 1.5 times above the upper reference value)
?History of hypersensitivity or allergic reaction to rupatadine or any other antihistamine compounds

?Presence of active cancer which requires chemotherapy or radiation therapy
?Presence of lactose and galactose intolerance or glucose-galactose malabsorption
?Simultaneous chronic spontaneous or physical urticaria that could interfere CCU clinical assessment.

?Intake of antihistamines or antileukotrienes within 7 days before beginning of the study

?Intake of oral or depot corticosteroids within 14 days prior to screening visit

?Use of systemic immunosupressants/immunomodulators like ciclosporine A, dapsone, methotrexate, mycophenolate, chloroquine, and comparable drugs within 28 days prior to screening visit.
?Use of ketoconazole, erythromycin or potential inhibitors of the isoenzyme CYP3A4 of the cytochrome P450

?Currently abusing drugs or alcohol

?Unwilling or unable to comply with the protocol

?Pregnancy or breast-feeding

?Sujetos que están en instituciones psiquiatritas, prisiones u otras instituciones similares. Ingreso previsto o actual en una institución tras estar de acuerdo con el párrafo 40 pasaje 1, numero 4 AMG.
?La presencia de enfermedades severas permanentes que afectan especialmente al sistema inmune, excepto urticaria y urticaria por frío.
?La presencia de enfermedades gastrointestinales permanentes las cuales puedan influenciar la terapia oral (diarrea crónica, malformaciones congénitas o mutilaciones quirúrgicas del tracto intestinal).
?Historia o presencia de epilepsia, desordenes neurológicos significativos, ataques cerebro-vasculares o isquemia.
?Historia o presencia de infarto de miocardio o arritmia cardíaca los cuales requieran terapia de medicamentos.
?Alteraciones de la repolarización del ECG (prolongaciones del QTc > 450ms)
?Presión sanguínea >180/100 mmHg y/o frecuencia cardíaca >100/min.
?Evidencia de enfermedad renal o hepática (GOT y/o GPT 3 veces superior al valor de referencia, creatinina sérica 1.5 veces superior al valor superior de referencia)

?Historia de hipersensibilidad o reacción alérgica a rupatadina o a otros compuestos antihistaminicos.

?Presencia de cáncer activo el cual requiera quimioterapia o terapia de radiación.
?Presencia de intolerancia a lactosa y galactosa o mala absorción de galactosa.
?Urticaria tanto crónica como espontánea simultáneamente, que pueda interferir con la evaluación de CCU

?Toma de antihistaminas o antileucotrienos dentro de los 7 días previos al inicio del ensayo.

?Toma de corticosteroides orales o depot dentro de los 14 días previos a la visita de screening.
?Uso de inmunosupresores/inmunomoduladores sistémicos tales como ciclosporina A, dapsona, metotrexato, micofenolato, cloroquina y medicamentos comparables dentro de los 28 días previos a la visita de screeening.
?Uso de ketoconazol, eritromicina o inhibidores potenciales del isoenzima CYP3A4 del citocromo P450.

?Abuso actual de drogas o alcohol.

?No desear o no ser capaz de cumplir con el protocolo.

?Embarazo o lactancia

E.5 End points

E.5.1

Primary end point(s)

-Change in critical stimulation time thresholds (CSTT) and critical temperature thresholds (CTT) after treatment with different dosages of rupatadine (20 mg and 40 mg) measured by Temptest® 3.0

-Cambio en el umbral del tiempo de estimulación (CSTT) y umbrales de temperatura critica (CTT) tras tratamiento con diferentes dosis de rupatadina (20 mg y 40 mg) medidos por Temptest® 3.0

E.5.1.1

Timepoint(s) of evaluation of this end point

Visit 2, visit 3, visit 4, visit 5

Visita 2, visita 3, visita 4, visita 5

E.5.2

Secondary end point(s)

-Change in mast cell mediator release, including histamine, PAF/LysoPAF and PGD2 after treatment with rupatadine (20 and 40 mg) compared to placebo
-Change in mast cell activation (measured by intracutaneous codeine, histamine and PAF injection)
-Safety and tolerability: This includes physical examination, routine safety laboratory assessments, clinical observation, vital signs and adverse event reporting

-Cambio en la liberación del mediador de los mastocitos, incluyendo histamina, PAF/LysoPAF y PGD2 tras tratamiento con rupatadina (20 y 40 mg) comparado con placebo.
-Cambio en la activación de mastocitos (medida por inyección de codeína intracutánea, histamina y de PAF).
-Seguridad y tolerabilidad. Esto incluye examen físico, valoraciones rutinarias de seguridad de laboratorio, observación clínica, signos vitales y reporte de efectos adversos.

E.5.2.1

Timepoint(s) of evaluation of this end point

Visit 3, visit 4, visit 5

Visita 3, visita 4, visita 5

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

E.8.1.6

Cross over

Yes

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Cruzado de tres vías

Three way crossover

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

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

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 subject last visit

Ultima visita del ultimo sujeto

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)

All patients included in the trial which may have ended their participation (either in an anticipated way or not) will be treated in Dermatology Service if needed.

A todos los pacientes que hayan sido incluidos en el ensayo clínico y que lo hayan finalizado (ya sea de manera anticipada o no) se les realizará un seguimiento en el Servicio de Dermatología.

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

2012-04-16

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-12-21

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-07-02

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