E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Actinic keratosis on the face or scalp |
queratosis actínicas en la cara o el cuero cabelludo |
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E.1.1.1 | Medical condition in easily understood language |
Actinic keratosis on the face or scalp |
queratosis actínicas en la cara o el cuero cabelludo |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10000614 |
E.1.2 | Term | Actinic keratosis |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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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 the efficacy of daily application for 3 consecutive days of ingenol mebutate gel 0.015% with the efficacy of diclofenac sodium gel 3% for 90 days in subjects with AK on the face or scalp. |
Comparar la eficacia de la aplicación diaria durante 3 días consecutivos de mebutato de ingenol en gel al 0,015% con la eficacia de diclofenaco sódico en gel al 3 % durante 90 días en pacientes con queratosis actínica (QA) en la cara o el cuero cabelludo. |
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E.2.2 | Secondary objectives of the trial |
To compare the efficacy of up to two treatment courses of ingenol mebutate gel 0.015% (daily application for 3 consecutive days) with the efficacy of diclofenac sodium gel 3% for 90 days in subjects with AK on the face or scalp. |
Comparar la eficacia de un máximo de dos ciclos de tratamiento con mebutato de ingenol en gel al 0,015% (aplicación diaria durante 3 días consecutivos) con la eficacia de diclofenaco sódico en gel al 3 % durante 90 días en pacientes con QA en la cara o el cuero cabelludo. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Following verbal and written information about the trial, the subject must provide informed consent documented by signing the Informed Consent Form (ICF) prior to any trial related procedures 2. Subjects with 4 to 8 clinically typical, visible and discrete AKs within a contiguous 25 cm² treatment area on the face or scalp |
1. Tras la información oral y escrita del ensayo, el paciente debe proporcionar el consentimiento informado, documentado mediante la firma del formulario de consentimiento informado (FCI) antes de realizar cualquier procedimiento relacionado con el ensayo. 2. Pacientes que presenten entre 4 y 8 QA aisladas, visibles y clásicas desde el punto de vista clínico, en una zona de tratamiento de 25 cm² contiguos en la cara o el cuello cabelludo. |
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E.4 | Principal exclusion criteria |
1. Location of the selected treatment area: ? on the periorbital skin ? on the perioral skin/around the nostrils ? within 5 cm of an incompletely healed wound ? within 10 cm of a suspected BCC or SCC or other neoplasia 2. Selected treatment area lesions that have atypical clinical appearance (e.g., hypertrophic, hyperkeratotic or cutaneous horn) or recalcitrant disease (e.g., did not respond to AK treatment in the previous) 3. History of SCC, BCC, malignant melanoma or other neoplasia in the selected treatmentarea 4. History or evidence of skin conditions other than the trial indication that would interfere with evaluation of the trial medication in the selected treatment area (e.g., eczema, unstable psoriasis, xeroderma pigmentosum) 5. Use of ingenol mebutate and/or diclofenac sodium in and within 5 cm of the selected treatment area within the last 12 months prior to Visit 1 6. Use of cosmetic or therapeutic products and procedures which could interfere with the assessments of the treatment area 7. Known or suspected hypersensitivity or allergy to any of the ingredients in ingenol mebutate gel or diclofenac sodium gel 8. Organ transplant recipients 9. Immunosuppressed subjects (for example HIV patients) 10. Clinical diagnosis/history or evidence of any medical condition that would expose a subject to an undue risk of a significant AE or interfere with assessments of safety and efficacy during the course of the trial, as determined by the investigator?s clinical judgment 11. Presence of acute sunburn within the selected treatment area 12. Current enrolment or participation in a clinical trial within 30 days of entry into this trial 13. Subjects previously randomised in the trial 14. Female subjects who are breastfeeding 15. Subjects who are institutionalized by court order or by the local authority 16. In the opinion of the investigator, the subject is unlikely to comply with the Clinical Study Protocol (e.g. alcoholism, drug dependency or psychotic state) |
1. Ubicación de la zona de tratamiento seleccionada: • en la piel periorbitaria • en la piel peribucal/alrededor de los orificios nasales • en los 5 cm alrededor de una herida que no se haya curado por completo • en los 10 cm alrededor de un presunto carcinoma de células basales (CCB) o carcinoma de células escamosas (CCE) u otra neoplasia. 2. Lesiones en el área de tratamiento seleccionada que tengan un aspecto clínico atípico (p.e. hipertróficas, hiperqueratósicas o cuerno cutáneo) o enfermedades recalcitrantes (p.e. no respuesta a tratamiento previo de QA) 3. Historia de SCC, BCC, melanoma maligno u otra neoplasia en el área de tratamiento seleccionada. 4. Historia o evidencia de problemas cutáneos que no sean los de la indicación del ensayo, los cuales interfieran en la evaluación de la medicación en el ensayo en el área de tratamiento seleccionada (p.e. eczema, psoriasis inestable, xeroderma pigmentosum). 5.Uso de ingenol mebutato y/o diclofenaco sódico en el área de tratamiento seleccionada y dentro de 5 cm del área de tratamiento seleccionada, dentro de los últimos 12 meses anteriores a la visita1. 6. Uso de cosméticos o productos terapéuticos y procedimientos, los cuales puedan interferir con las valoraciones del área de tratamiento. 7. Hipersensibilidad conocida o sospechada de alergia a cualquiera de los componentes de ingenol mebutato gel o diclofenaco sódico gel. 8. Receptores de órganos transplantados 9. Sujetos inmunodeprimidos (por ejemplo pacientes con HIV) 10. Diagnostico clínico/historia o evidencia de alguna afección médica que pueda exponer al sujeto a un riesgo innecesario o a un AA significativo o interferir con valoraciones de seguridad y eficacia durante el curso del ensayo, tal y como esté determinado por el criterio del investigador. 11. Presencia de quemaduras solares agudas en el área de tratamiento selecionada 12. Reclutamiento actual o participación en un ensayo clínico dentro de los 30 días de entrar en éste ensayo. 13. Sujetos previamente randomizados en el ensayo 14. Sujetos femeninos que estén lactando 15. Sujetos que estén encarcelados por orden judicial o por la autoridad local 16. En opinión del investigador, un sujeto que a duras penas pueda cumplir con el protocolo del ensayo (p.e. alcoholismo, drogodependientes o estados psicóticos) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Complete clearance of all AKs in the treatment field at Week 8 for ingenol mebutate gel 0.015% and Week 17 for diclofenac sodium gel 3% |
Remisión completa de todas las QA en la zona de tratamiento en la semana 8 con mebutato de ingenol en gel al 0,015 % y en la semana 17 con diclofenaco sódico en gel al 3 %. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Evaluation at week 8 for ingenol mebutate gel 0.015%. Evaluation at week 17 for diclofenac sodium gel 3%. |
Evaluación en la semana 8 para ingenol mebutato gel 0.015% Evaluación en semana 17 para diclofenaco sódico gel 3% |
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E.5.2 | Secondary end point(s) |
As secondary response criteria, complete clearance at Week 17 for diclofenac sodium gel 3% will be compared with the following three measures of complete clearance in the ingenol mebutate 0.015% group: - Complete clearance of all AKs in the treatment field after one or two ingenol mebutate treatment courses. Subjects receiving only one treatment course are evaluated at Week 8 and subjects receiving two treatment courses are evaluated at Week 17. - Complete clearance of all AKs in the treatment field at Week 17 - Complete clearance of all AKs in the treatment field at Week 17 following only one ingenol mebutate treatment course. Subjects receiving a second ingenol mebutate treatment course are considered non-cleared. |
Como criterios de respuesta secundarios, se comparará la remisión completa en la semana 17 con diclofenaco sódico en gel al 3 % con las tres medidas siguientes de remisión completa en el grupo de mebutato de ingenol al 0,015 %: • Remisión completa de todas las QA en la zona de tratamiento tras uno o dos ciclos de tratamiento con mebutato de ingenol. Los pacientes que solo reciben un ciclo de tratamiento se evalúan en la semana 8 y los pacientes que reciben dos ciclos de tratamiento se evalúan en la semana 17. • Remisión completa de todas las QA en la zona de tratamiento en la semana 17 • Remisión completa de todas las QA en la zona de tratamiento en la semana 17 tras un solo ciclo de tratamiento con mebutato de ingenol. Los pacientes que reciben un segundo ciclo de tratamiento con mebutato de ingenol, se considera que no presentan remisión de las lesiones. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Evaluation at week 17 for diclofenac sodium gel 3% (all secondary endpoints). For ingenol mebutate gel 0.015%: 1st secondary endpoint: Evaluation at week 8 for subjects receiving one treatment course, evaluation at week 17 for subjects receiving two treatment courses. 2nd secondary endpoint: Evaluation at week 17. 3rd secondary endpoint: Evaluation at week 17 for subjects receiving one treatment course, evaluation at week 8 for subjects receiving two treatment courses. |
Evaluación en la semana 17 para diclofenaco sódico gel 3% (todos los objetivos secundarios). Para ingenol mebutato gel 0.015%: 1º objetivo secundario: Evaluación en semana 8 para sujetos que reciben un tratamiento, evaluación en la semana 17 para sujetos que reciben dos tratamientos. 2º objetivo secundario: Evaluación en la semana 17 3º objetivo secundario: Evaluación en semana 17 para sujetos que reciben mas de un tratamiento, evaluación en la semana 8 para sujetos que reciben dos tratamientos. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
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) | No |
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 | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 34 |
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 sujeto |
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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 | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 12 |