E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Children Superficial Hemangioma |
Hemangioma Infantil Superficial |
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E.1.1.1 | Medical condition in easily understood language |
Children Superficial Hemangioma |
Hemangioma Infantil Superficial |
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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 determine the efficacy of timolol maleate 0.5% solution in the treatment of infantile hemangiomas surface during the early proliferative stage. |
Analizar la eficacia del timolol maleato 0.5% en solución en la involución del hemangioma infantil en fase proliferativa temprana. |
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E.2.2 | Secondary objectives of the trial |
- To analyze the effectiveness of timolol maleate 0.5%, expressed as complete / almost complete resolution of the HI at week 4, 12 and 24 compared to baseline. - To analyze the effectiveness of timolol maleate 0.5% by qualitative assessments in the center by parents or guardians - To analyze the persistence of efficacy 12 weeks after end of treatment - To analyze the safety profile and local tolerability of timolol maleate 0.5% solution in the treatment of HI |
- Analizar la eficacia de timolol maleato 0.5%, expresada como resolución completa/casi completa del HI en la semana 4, 12 y 24 en comparación con el período basal. - Analizar la eficacia de timolol maleato 0.5% mediante las evaluaciones cualitativas realizadas en el centro por los padres o tutores - Analizar la persistencia de la eficacia 12 semanas después del final del tratamiento - Analizar el perfil de seguridad y la tolerabilidad local del timolol maleato 0.5% solución en el tratamiento del HI |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Informed Consent signed by a parent or guardian of the patient, both for study participation and for taking pictures. - The patient is 10 to 60 days old at the time of inclusion. - The patient should have at least: - A mixed both surface, sized from 0.3 to 5 cm in any location of the body surface focal or segmental hemangioma.; or - A hemangioma precursor defined as pink macules with white halo in periphery, clinically characteristic of the precursors of hemangiomas in infancy; or - A "abortion" or minimum defined as angiomas proliferation telangiectatic Hemangioma showing proliferation in <5% of the surface of the hemangioma |
- Firma de Consentimiento Informado por parte de los padres o tutores del paciente, tanto para la participación en el estudio como para la toma de fotografías. - El paciente debe de tener de 10 a 60 días de vida en el momento de inclusión. - El paciente deberá tener al menos: - Un hemangioma focal o segmentario, tanto superficiales como mixtos, de un tamaño entre 0,3 y 5 cm., en cualquier localización de la superficie corporal; o - Un precursor de hemangioma definido como máculas rosadas con halo blanquecino en periferia, clínicamente característico de los precursores de los hemangiomas en la infancia; o - Un Hemangioma ?abortivo? o de proliferación mínima definidos como angiomas telangiectásicos que muestran una proliferación en < 5% de la superficie del hemangioma |
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E.4 | Principal exclusion criteria |
- Patients under 10 and over 60 days old at the time of inclusion. - Patients with indication of systemic therapy (ulcerated hemangiomas in mucosal surfaces, disfiguring) - Patients who are with another treatment modality for hemangiomas (beta blockers, corticosteroids, interferon, cyclophosphamide, vincristine) - Hemangiomas associated syndromes (PHACE, LUMBAR, SACRAL, PELVIS) - Hemangiomas affecting any organ or airway - Hemangiomas affecting any organ or airway - Patients with any underlying disease (bronchial asthma, severe lung disease, sinus bradycardia, atrioventricular block second degree, third degree, overt heart failure or cardiogenic shock). - Patients with congenital defects (patients with a chromosomal syndrome, patients with congenital heart disease (tetralogy of Fallot, transposition of the great arteries, ventricular septal defect, atrial septal defect, persistent ductus arteriosus) - Patients with neoplastic disease (leukemias, sarcomas, neuroblastoma, retinoblastoma, etc.) - Hypersensitivity to the active substance or any of the excipients. |
- Pacientes con menos de 10 y más de 60 días de vida en el momento de la inclusión. - Pacientes con indicación de terapia sistémica (hemangiomas ulcerados, en superficies mucosas, desfigurantes) - Pacientes que se encuentren con otra modalidad de tratamiento para hemangiomas (betabloqueantes, corticosteroides, interferón, ciclofosfamida, vincristina) - Hemangiomas asociados a Síndromes (PHACE, LUMBAR, SACRAL, PELVIS) - Hemangiomas que afecten algún órgano o vía aérea - Pacientes con alguna enfermedad de base (asma bronquial, enfermedad pulmonar grave, bradicardia sinusal, bloqueo auriculoventricular de segundo grado y tercer grado, insuficiencia cardiaca manifiesta o shock cardiogénico). - Pacientes con defectos congénitos (pacientes con algún síndrome cromosómico, pacientes con enfermedad cardiaca congénita (tetralogía de Fallot, transposición de grandes vasos, Comunicación interventricular, Comunicación interauricular, persistencia del ducto arterioso) - Pacientes con patología oncológica (Leucemias, sarcomas, neuroblastoma, retinoblastoma, etc) - Hipersensibilidad al principio activo o algunos de los excipientes. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for evaluating the efficacy of treatment is complete / almost complete resolution of the HI target at week 24 of treatment, which is defined as complete resolution of the lesion complete improvement and almost complete resolution is defined as the existence of a minimum degree of telangiectasia, erythema, dermal thickening, soft tissue swelling and / or distortion of anatomical references. |
La variable principal para evaluar la eficacia del tratamiento es la resolución completa/ casi completa del HI diana a la semana 24 de tratamiento, donde resolución completa se define como mejoría completa de la lesión y resolución casi completa se define como existencia de un grado mínimo de telangiectasia, eritema, engrosamiento cutáneo, tumefacción de partes blandas y/o distorsión de referencias anatómicas. |
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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) |
- Centralized independent qualitative assessments - Independent qualitative evaluations by the Investigator - Qualitative evaluations by parents / guardians |
- Evaluaciones cualitativas independientes centralizadas - Evaluaciones cualitativas independientes realizadas por el Investigador - Evaluaciones cualitativas realizadas por los padres/tutores |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
4, 8, 12 and 24 weeks |
4, 8, 12 y 24 semanas |
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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 | 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) | 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 | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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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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 | 24 |
E.8.9.1 | In the Member State concerned days | |