E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Spontaneous Urticaria |
Urticaria crónica espontánea |
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E.1.1.1 | Medical condition in easily understood language |
Chronic Spontaneous Urticaria |
Urticaria crónica espontánea |
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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 compare CSU disease activity at the end of the follow up phase between patients that had been treated daily continuously vs. on-demand in the treatment phase. |
Comparar la actividad de la urticaria crónica espontanea (CSU) al final de la fase de seguimiento, entre los pacientes que han sido tratados con terapia diaria continuada y los que han sido tratados con terapia a demanda. |
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E.2.2 | Secondary objectives of the trial |
-To compare CSU disease activity during the follow up phase between patients with response vs. non-response at the end of the treatment phase. -To compare CSU disease activity during the follow up phase between patients that had been treated daily continuously vs. on-demand in the treatment phase. -To compare the efficacy of rupatadine 10 mg during the treatment phase between patients treated daily continuously vs. on-demand. -To assess the efficacy of rupatadine 20 mg in CSU patients who not show complete symptom control with the 10 mg dose. -Evaluation of the safety profile of the rupatadine 20 mg dose. |
-Comparar la actividad de la CSU, durante la fase de seguimiento entre los pacientes con respuesta y los pacientes sin respuesta al final de la fase de tratamiento. -Comparar la actividad de la CSU entre los pacientes tratados diariamente en la fase de seguimiento y aquellos tratados a demanda. -Comparar la eficacia de rupatadina 10 mg entre los pacientes tratados diariamente y aquellos tratados a demanda durante la fase de tratamiento. -Evaluar la eficacia de rupatadina 20 mg en pacientes con CSU que no muestran un control completo de los síntomas con la dosis de 10 mg. -Evaluación del perfil de seguridad de la dosis de rupatadina 20 mg. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Male or female aged 18 years and older -Documented history of active CSU (urticaria and wheals) with or without an associated angioedema for at least three days per week over the last 6 weeks prior to visit 1 (screening). Urticaria symptoms must comprise wheals and itch -UAS7 of >=6 during the screening phase -Overall duration of chronic spontaneous urticaria for at least 3 months -Informed consent signed and dated -Able to read, understand and willing to sign the informed consent form and abide with study procedures -Willing, committed and able to return for all clinic visits and complete all study-related procedures -In females of childbearing potential: negative pregnancy test; females willing to use highly effective contraception (Pearl-Index < 1) a woman will be considered not of childbearing potential if she is post-menopausal for > 2 years or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy) -No participation in other clinical trials 4 weeks before and after participation in this study |
-Varones o mujeres de 18 o más años de edad. -Historia documentada de CSU activa (urticaria y habones) con o sin un angioedema asociado como mínimo 3 días por semana durante las últimas 6 semanas previas a la visita 1 (screening). Los síntomas de urticaria han de presentar habones y picor. -UAS7 de >=6 durante la fase de screening -Duración total de la urticaria crónica espontánea de al menos 3 meses. -Consentimiento informado firmado y fechado. -Ser capaz de leer, entender y tener intención de firmar el consentimiento informado y consentir con los procedimientos del ensayo. -Con voluntad, comprometido y capaz de volver al centro para las visitas clínicas y completar todos los procedimientos propios del ensayo. -En mujeres fértiles: test de embrazo negativo, que usen métodos contraceptivos altamente efectivos (Pearl-Index < 1): una mujer será considerada no fértil si es post-menopáusica durante más de 2 años o estéril quirúrgicamente (ligamento tubal bilateral, ooferoctomía bilateral o histerectomía). -No haber participado en otros ensayos clínicos durante las 4 semanas anteriores a la participación en este ensayo. |
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E.4 | Principal exclusion criteria |
-Chronic spontaneous urticaria patients with a known resistance to nsAH in 4 times the licensed doses -Chronic spontaneous urticaria patients with a known resistance to rupatadine -Isolated presence or domination of inducible forms of urticaria or cholinergic urticaria (no chronic spontaneous urticaria) -History of adverse reactions to rupatadine or known hypersensitivity to rupatadine or its ingredients -Intake of oral corticosteroids or intravenously applied corticosteroids within 28 days prior to screening visit -Use of depot corticosteroids within 3 months prior to screening visit (inhaled corticosteroids are allowed) -Use of systemic immunosupressants/immunomodulators such as ciclosporin, dapsone, metotrexate, and comparable drugs within 28 days prior to screening visit. -Significant medical condition, in the opinion of the Investigator, rendering the patient immunocompromised or not suitable for a clinical trial -Significant concomitant illness, in the opinion of the Investigator, that would adversely affect the subject?s participation or evaluation in this study -Subjects for whom there is concern, in the opinion of the Investigator, about compliance with the protocol procedures -The presence of a permanent gastrointestinal condition which may influence the oral therapy (chronic diarrhoea diseases, congenital malformations or surgical mutilations of gastrointestinal tract) -Presence of active cancer which requires chemotherapy or radiation therapy -History or presence of epilepsy, significant neurological disorders, cerebrovascular attacks or ischemia -History or presence of myocardial infarction or acute myocardial ischemia -History or presence of cardiac arrhythmia which requires drug therapy -History or presence of clinically significant bradycardia (<50 bpm) -ECG alterations of repolarisation (QTc prolongations >450ms in females, >430ms in males) -Blood pressure >180/100 mmHg and/or heart rate >100/min -Presence of uncorrected hypokalemia or hyperkalemia -Evidence of significant hepatic or renal disease (GOT and/or GPT >2 times above the upper reference value, serum creatinine 1.5 times above the upper reference value) -Presence of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption -Medication with HMG-CoA reductase inhibitors (statins) -Presence of alcohol abuse or drug addiction -Pregnancy or breast-feeding -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). |
-Pacientes con urticaria crónica espontánea, con resistencia conocida a nsAH de 4 veces las dosis prescritas. -Pacientes con urticaria crónica espontánea, con resistencia conocida a Rupatadina. -Presencia aislada o dominancia de formas inducibles de urticaria o urticaria colinérgica (no urticaria crónica espontánea). -Historia de reacciones adversas a rupatadina o hipersensibilidad conocida al producto o a alguno de sus excipientes. -Toma de corticoesteroides orales o bien corticoesteroides aplicados por vía intravenosa dentro de los 28 días anteriores a la visita de screening. -Uso de corticoesteroides depot dentro de los 3 meses previos a la visita de screening (se permiten los corticoesteroides inhalados). -Uso de inmunosupresores/inmunomoduladores sistémicos tales como ciclosporina, dapsona, metotrexato y fármacos comparables, dentro de los 28 días previos a la visita de screening. -Enfermedad significativa que, a criterio del investigador, lleve al paciente a estar inmunodeprimido, o no se considere adecuado para el ensayo. -Enfermedad concomitante significativa que, en opinión del investigador, pudiera afectar negativamente en la participación y la evaluación de los datos del paciente en el ensayo. -Sujetos sobre los cuales haya dudas, según el investigador, de que cumplan con los prodecimientos del protocolo. -Presencia de enfermedad gastrointestinal permanente, la cual pueda interferir en la administración oral (diarrea crónica, malformaciones congénitas o mutilaciones quirúrgicas del tracto gastrointestinal). -Presencia de cáncer activo que requiera quimioterapia o radioterapia. -Historia o presencia de epilepsia, trastornos neurológicos significativos, ataques cerebrovasculares o isquemia. -Historia o presencia de infarto de miocardio o isquemia de miocardio aguda. -Historia o presencia de arritmia cardiaca que requiere la terapia con medicamentos. -Historia o presencia de bradicardia clínicamente significativa (<50 ppm). -Alteraciones del ECG de repolarización (prolongaciones de QTc> 450 ms en mujeres,> 430ms en varones). -Presión arterial> 180/100 mmHg y / o frecuencia cardíaca> 100/min. -Presencia de hipopotasemia no corregida o hiperpotasemia. -Evidencia de enfermedad hepática o renal significativa (GOT y / o GPT> 2 veces por encima del valor de referencia superior, creatinina sérica 1,5 veces por encima del valor de referencia superior). -Presencia de intolerancia a la galactosa, deficiencia de lactasa de Lapp o malabsorción de glucosa-galactosa. -Medicación con inhibidores de la HMG-CoA reductasa (estatinas) -Presencia de abuso de alcohol o adicción a drogas. -Embarazo o lactancia. -Sujetos ingresados en centros psiquiátricos, prisiones, u otras instituciones similares. Ingreso próximo o presente en una institución tras cumplir con el § 40 párrafo 1, numero 4 AMG (Arzneimittelgesetz). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Comparison of the UAS7 values (change from baseline) at the end of the follow-up phase between patients that had been treated daily continuously vs. on-demand in the treatment phase. |
Comparación de los valores de UAS7 (cambio respecto el basal), al final de la fase de seguimiento entre aquellos pacientes que han sido tratados diariamente, y aquellos que han sido tratados a demanda durante la fase de tratamiento |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
-Comparison of the UAS7 values (change from baseline) during the follow-up phase between patients with response vs. non-response at the end of the treatment phase. -Comparison of the UAS7 values (change from baseline) during the follow-up phase (period from week 10 to week 14) between patients that had been treated daily continuously vs. on-demand in the treatment phase. -Comparison of the UAS7 values (change from baseline) during the treatment phase (week 4, treatment with rupatadine 10 mg) between patients treated daily continuously vs. on-demand. -Comparison of the UAS7 values (change from baseline) during the treatment phase between patients treated daily continuously vs. on demand during weeks 5 to 10. -Comparison of the UAS7 values during treatment with rupatadine 10 mg and treatment with rupatadine 20 mg in patients who received an updosing of rupatadine (paired analysis). -Comparison of the proportion of patients with response (based on the UAS7) during the follow up phase in patients treated daily continuously vs on-demand in the treatment phase and in patients with response vs. non-response at the end of the treatment phase. -Assessment of the safety and tolerability of rupatadine 20 mg (based on the physical examinations, vital signs, clinical observations, monitoring lab, and adverse event reporting) |
-Comparación de los valores UAS7 (cambio respecto el basal), durante la fase de seguimiento, entre los pacientes con respuesta y aquellos sin respuesta al final de la fase de tratamiento. -Comparación de los valores UAS7 (cambio respecto el basal), durante la fase de seguimiento (periodo desde la semana 10 a la semana 14), entre los pacientes que han sido tratados diariamente frente a aquellos tratados a demanda durante la fase de tratamiento. -Comparación de los valores UAS7 (cambio respecto el basal), durante la fase de tratamiento (semana 4, tratamiento con rupatadina 10 mg) entre pacientes tratados diariamente frente a aquellos con tratados a demanda. -Comparación de los valores UAS7 (cambio respecto el basal), durante la fase de tratamiento, entre pacientes tratados diariamente frente a aquellos tratados a demanda, durante las semanas 5 a 10. -Comparación de los valores UAS7 durante el tratamiento con rupatadina 10 mg y el tratamiento con rupatadina 20 mg en pacientes que recibieron una dosis superior de rupatadina (análisis pareado). -Comparación de la proporción de pacientes con respuesta (basada en el UAS7), durante la fase de seguimiento en pacientes tratados continuamente frente a aquellos tratados a demanda en la fase de tratamiento y en pacientes con respuesta frente a aquellos sin respuesta al final de la fase de tratamiento. -Evaluación de la seguridad y tolerabilidad de rupatadina 20 mg (en base a los exámenes físicos, signos vitales, observaciones clínicas, laboratorio de monitorización y notificación de reacciones adversas) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Weeks 11-16, Weeks 11-14, Week 4, Weeks 5-10, Week 4 vs. Week 10, Weeks 11-16 |
Semanas 11-16, semanas 11-14, semana 4, semanas 5-10, semana 4 vs. semana 10, semanas 11-16 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.7 | Other | No |
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 | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
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
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LVLS |
Última visita del último paciente |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |