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 | No |
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 | No |
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. |
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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. |
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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 | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |