E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Multiple sclerosis |
Esclerosis múltiple |
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E.1.1.1 | Medical condition in easily understood language |
Multiple sclerosis |
Esclerosis múltiple |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028245 |
E.1.2 | Term | Multiple sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system 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 assess the non-inferiority of clinical and radiological efficacy of the treatment with lower-high dose of oMP (625mg/day for 3 days) vs high dose of oMP (1250mg/day for 3 days) in patients in relapse of MS, 28 days after the treatment. |
Evaluar la no inferioridad de la eficacia clínica y radiológica del tratamiento con una megadosis menos alta (625mg/24h) de MP administrada durante 3 días por vía oral versus megadosis más alta (1250mg/24) de MP administrada durante 3 días por vía oral en pacientes en brote de EM. |
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E.2.2 | Secondary objectives of the trial |
To assess the safety, tolerability and quality of life of both doses. |
Evaluar la seguridad, tolerabilidad y calidad de vida de ambas pautas. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Relapsing-remitting MS (Mc Donald criteria 2010) regardless being under immunomodulatory treatment
2. EDSS (previous to relapse) between 0 and 5
3. MS relapse of moderate intensity (EDSS increase from 1 to 2.5 points) or severe intensity (EDSS increase > 3 points)
- If EDSS previous relapse is available:
• optic neuritis, myelitis or brainstem relapse: the EDSS should increase of 1 point in visual, pyramidal or brainstem system function
• relapse in other location or uncertain location: the EDSS should increase at least 1 point
- If EDSS previous relapse is not available:
• optic neuritis, myelitis or brainstem relapse: the visual, pyramidal or brainstem system function should be > 2 points.
• relapse in other location or uncertain location: EDSS should be > 2 points
4. Recent clinical relapse onset (<15 days) without fever
5. One month of clinical stability prior to relapse
6. Signed informed consent
7. Capacity to ingest the medication.
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1. Estar diagnosticado de EM Remitente Recurrente según los criterios de Mc Donald 2010
2 . Tener un EDSS previo al brote entre 0 y 5
3. Tener un brote de EM de intensidad moderada (aumento EDSS 1-2,5 puntos) o grave (aumento EDSS > 3 puntos):
- en los casos en los que se disponga de un EDSS previo al brote actual:
o si el brote consiste en una neuritis óptica, un síndrome de tronco o una mielitis, el EDSS ha debido de aumentar al menos 1 punto en el sistema funcional visual, de tronco o piramidal
o si el brote es de otra localización o localización incierta, el EDSS debe aumentar al menos 1 punto
- en los casos en los que no se disponga de un EDSS previo al brote actual:
o si el brote consiste en una neuritis óptica, un síndrome de tronco o una mielitis, el EDSS debe de puntuar > 2 puntos en el sistema funcional visual, de tronco o piramidal
o si el brote es de otra localización o localización incierta, el EDSS debe puntuar > 2 puntos en los brotes de otra topografía o topografía incierta
4. Ausencia de fiebre
5. Los síntomas han aparecido tras al menos un mes de estabilidad previa
6. Firma del consentimiento informado a participar en el estudio antes de iniciar cualquier procedimiento propio del estudio
7. Capacidad y voluntad para poder ingerir la medicación. |
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E.4 | Principal exclusion criteria |
1. Doubts about the diagnosis of multiple sclerosis
2. First episode of inflammatory neurological disease
3. Secondary progressive MS or primary progressive MS
4.Symptoms with lasted less than 24 hours of evolution
5. Any degree of subjective or objective remission
6. Treatment with corticosteroids during the previous 30 days
7. Patients with immunosuppressive treatment (azathioprine, mitoxantrone, cyclophosphamide) or Natalizumab or Fingolimod
8. Pregnancy or breastfeeding women or women of childbearing potential not using contraceptive measures
9. Diseases with a contraindication of treatment with corticosteroids
10. History of serious adverse reaction or hypersensitivity to drugs related to study medication
11. Patients who could not be regular MRI, not collaborators or who requires anesthesia.
12. Lactose intolerance
13. Patients with allergies to contrast used in MRI
14. Patients with renal impairement |
1. Existencia de dudas respecto al diagnóstico de esclerosis múltiple
2. Primer episodio inflamatorio neurológico (brote)
3.Esclerosis múltiple secundaria progresiva o primaria progresiva
4.Síntomas que hayan durado menos de 24 horas
5. Cualquier grado de remisión subjetiva u objetiva
6. Estar en tratamiento o haber sido tratado con corticoides en los 30 días anteriores
7. Pacientes en tratamiento con inmunosupresores (azatioprina, mitoxantrona, ciclofosfamida) o que hayan recibido Natalizumab o Fingolimod
8. Embarazo o lactancia o mujeres en edad fértil que no utilicen medidas contraceptivas
9. Enfermedades que contraindiquen el tratamiento con corticoides
10. Antecedentes de reacción adversa grave o de hipersensibilidad a fármacos relacionados con la medicación a estudio
11. Pacientes que no pudieran realizarse de forma periódica exploraciones de RM, pacientes no colaboradores o que requieran anestesia
12. Pacientes intolerantes a la lactosa
13. Pacientes con alergia al contraste utilizado en la RM
14. Pacientes con insuficiencia renal conocida. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
- To assess the non-inferiority in the improvement in relapse based on a margin of 1 on the EDSS disability scale of Kurtzke
- and radiological: MRI improvement in the number of MRI lesions and gadolinium enhancement (Gd +) |
- Evaluación de la no-inferioridad en la mejoría del brote en base a un margen de no-inferioridad de 1 en la escala EDSS mediante la escala de valoración de discapacidad de Kurtzke
- Mejoría del número de lesiones y en el realce de gadolinio (Gd+) en la RM cerebral |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline, day 8 and day 29 |
Basal, día 8 y día 29 |
|
E.5.2 | Secondary end point(s) |
- Adverse events / tolerability
- Questionnaires MSQOL-54 and MFIS |
- Acontecimientos adversos / Tolerabilidad
- Cuestionarios MSQol-54 y MFIS |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline, day 8 and day 29 |
Basal, día 8 y día 29 |
|
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 | 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 | 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 | 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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Diferente dosis de metilprednisolona administrados por vía oral |
Different dossage of methylprednisolone administered orally |
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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 | 9 |
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 | 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 |