| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic schizophrenia |
| Esquizofrenia crónica |
|
| E.1.1.1 | Medical condition in easily understood language |
| Chronic schizophrenia |
| Esquizofrenia crónica |
|
| E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10039626 |
| E.1.2 | Term | Schizophrenia |
| E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
| 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 evaluate the safety and tolerability (including EEG and ECG effects) of an oral dose of evenamide of 30 mg bid [60 mg/day]), achieved after a 1-week titration starting with 15 mg bid, compared to placebo, in patients with schizophrenia who are being treated with stable doses of antipsychotic medication (aripiprazole, clozapine, quetiapine, olanzapine, paliperidone or risperidone).
-To evaluate the efficacy of evenamide at a dose of 30 mg bid, achieved after a 1-week titration starting with 15 mg bid, compared to placebo, based on improvements in symptoms of schizophrenia, as assessed by the Positive and Negative Syndrome Scale (PANSS) total score. |
-Evaluar la seguridad y tolerabilidad (incluidos los efectos del EEG y el ECG) de una dosis oral de 30 mg de evenamida dos veces al día [60 mg/día]), lograda después de un ajuste posológico de 1 semana comenzando con 15 mg dos veces al día, en comparación con placebo, en pacientes con esquizofrenia que están siendo tratados con dosis estables de fármacos antipsicóticos (aripiprazol, clozapina, quetiapina, olanzapina, paliperidona o risperidona).
-Evaluar la eficacia de la evenamida a una dosis de 30 mg dos veces al día, lograda tras un ajuste posológico de 1 semana comenzando con 15 mg dos veces al día, en comparación con el placebo, en función de las mejoras en los síntomas de la esquizofrenia, evaluadas mediante la puntuación total de la Escala de síndromes positivos y negativos
(Positive and Negative Syndrome Scale, PANSS). |
|
| E.2.2 | Secondary objectives of the trial |
-To evaluate the efficacy of evenamide at a dose of 30 mg bid, achieved after a 1-week titration starting with 15 mg bid, compared to placebo, based on improvements in symptoms of schizophrenia, as assessed by the Clinical Global Impression - Severity of illness (CGI-S)
-To evaluate the efficacy of evenamide at a dose of 30 mg bid, achieved after a 1-week titration starting with 15 mg bid, compared to placebo, based on improvements in symptoms of schizophrenia, as assessed by the CGI - Change from baseline (CGI-C)
-To determine the multiple-dose pharmacokinetics (PK) of evenamide and its major metabolite, (3-butoxy-phenyl)-acetic acid, at a dose of 30 mg bid
-To determine the effect of evenamide, compared to placebo, on daily functioning, based on improvements on the Strauss-Carpenter Level of Functioning (LOF) scale
-To determine the patient’s satisfaction with treatment, compared to their previous treatment, based on improvements on the Medication Satisfaction Questionnaire (MSQ) |
-Evaluar la eficacia de evenamida 30mg bid, lograda tras un ajuste
posológico de 1 semana comenzando con 15mg bid, en comparación con placebo, en función de las mejoras en los síntomas de la esquizofrenia, evaluadas por la Impresión clínica global de gravedad de la enfermedad
-Evaluar la eficacia de evenamida 30mg bid, lograda tras un ajuste
posológico de 1 semana comenzando con 15mg bid, en comparación con el placebo, en función de las mejoras en los síntomas de la esquizofrenia, evaluadas por el CDI, Cambio desde el inicio
-Determinar la farmacocinética de dosis múltiples de evenamida y su
metabolito principal, el ácido acético, con 30mg bid
-Determinar el efecto de la evenamida, comparado con placebo, sobre el funcionamiento diario, en función de las mejoras en la escala del nivel de funcionamiento de Strauss-Carpente
-Determinar la satisfacción del paciente con el tratamiento, en
comparación con su tratamiento previo, en función de las mejoras en el Cuestionario de satisfacción |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Has a current diagnosis of schizophrenia in accordance with DSM-5. Other Axis-I disorders may be present only as lifetime diagnoses if they are not relevant to the current episode of schizophrenia. [see Exclusion criteria]
- Has been treated with antipsychotics for at least 2 years.
- Has a total score on the PANSS ≥70 and ≤85.
- Has a score of 4 (moderate) or more on at least 2 of the following 4 core symptoms of psychosis: conceptual disorganization, hallucinatory behavior, suspiciousness and unusual thought content; and a total score of at least 20 on the combined total of the 4 core items and the following 3 additional positive symptoms items: grandiosity, hostility, and excitement (based on the PANSS descriptions).
- Has a Clinical Global Impression – Severity of disease (CGI-S) rating of moderately, moderately severely, or severely ill (score of 4, 5 or 6).
- Needs antipsychotic treatment and is currently receiving a stable dose (minimally for 4 weeks prior to screening) of aripiprazole, clozapine, quetiapine, olanzapine, paliperidone, or risperidone (at least 2 mg risperidone dose-equivalent).
- Current symptoms have been stably present for at least one month. |
-Tiene un diagnóstico actual de esquizofrenia de acuerdo con el DSM-5.
Otros trastornos del Eje I pueden estar presentes solo como diagnósticos de por vida si no son relevantes para el episodio actual de esquizofrenia, [ver Criterios de exclusión]
-Se ha tratado con antipsicóticos durante al menos 2 años
-Tiene una puntuación total en la PANSS ≥70 y ≤85
-Tiene una puntuación de 4 (moderada) o más en al menos 2 de los
siguientes 4 síntomas principales de psicosis: desorganización
conceptual, comportamiento alucinante, sospecha y contenido de
pensamiento inusual; y una puntuación total de al menos 20 en el total combinado de los 4 elementos principales y los siguientes 3 elementos adicionales de síntomas positivos: grandiosidad, hostilidad y excitación (basado en las descripciones combinadas de la PANSS)
-Tiene una puntuación de impresión clínica global - gravedad de la
enfermedad (Clinical Global Impression - Severity of disease, CGI-S) de moderada, moderadamente grave o gravemente enferma (puntuación de 4, 5 o 6)
-Necesita tratamiento antipsicótico y está recibiendo actualmente una dosis estable (mínimo durante 4 semanas antes de la selección) de aripiprazol, clozapina, quetiapina, olanzapina, paliperidona o risperidona (al menos 2 mg de risperidona equivalente a la dosis)
-Los síntomas actuales han estado presentes de forma estable durante al menos un mes |
|
| E.4 | Principal exclusion criteria |
- DSM-5 diagnosis of schizophreniform disorder (295.40), schizoaffective disorder (295.70), or other primary psychiatric diagnosis, such as bipolar disorder or major depressive disorder. (Comorbid depression will be assessed at screening and baseline using the Calgary Depression Scale for Schizophrenia [CDSS]. A score of 7 or higher will be exclusionary.)
- History (within three months of study entry) or current diagnosis of Substance Use Disorder as defined by the DSM-5 criteria, with a severity of ‘moderate’ or ‘severe’, or patient is currently abusing drugs or alcohol or has done so in the past year. A history of nicotine or caffeine dependence is acceptable
- Severity of current episode of psychosis requires that the patient be hospitalized. Patients who are chronically hospitalized or in psychiatric day-care, whose hospitalization is for logistic reasons and not due to the severity of their illness, will be eligible for the study.
- Has a score of 6 (severe) or higher on 2 or more of the following 4 core symptoms of psychosis: conceptual disorganization, hallucinatory behavior, suspiciousness and unusual thought content (derived from the PANSS).
- Severity of psychosis is rated severe or higher (CGI-S of 7).
- Known suicidal risk. Patients who have exhibited suicidal behaviour within the past 6 months, as indicated by an actual attempt, interrupted attempt, aborted attempt, or preparatory acts will be excluded from participating in the trial.
- “Treatment resistant” defined significant persistent symptoms of schizophrenia after adequate doses of two standard antipsychotic medications (from two different chemical classes, including at least one atypical antipsychotic) following 6 weeks of treatment with each at adequate doses. Treatment resistant patients on clozapine for at least 6 months will be permitted if they have shown minimal improvement in the Investigator’s judgement. |
-Diagnóstico DSM-5 de trastorno esquizofrénico (295,40), trastorno
esquizoafectivo (295,70) u otro diagnóstico psiquiátrico primario, como trastorno bipolar o trastorno depresivo mayor. (La depresión comórbida se evaluará en la selección y al inicio utilizando la Escala de depresión de Calgary para la esquizofrenia. Una puntuación de 7 o superior será motivo de exclusión)
-Antecedentes (en los tres meses previos a la entrada en el estudio) o
diagnóstico actual de trastorno por consumo de sustancias según lo definido por los criterios DSM-5, con una gravedad de "moderada" o
"grave", o el paciente está abusando actualmente de drogas o alcohol, o lo ha hecho en el último año. Es aceptable tener antecedentes de nicotina o dependencia de la cafeína
-La gravedad del episodio actual de psicosis requiere la hospitalización del paciente. Los pacientes hospitalizados de forma crónica o en cuidados psiquiátricos de día, cuya hospitalización se deba a motivos logísticos y no a la gravedad de su enfermedad, serán aptos para el estudio
-Tiene una puntuación de 6 (grave) o superior en 2 o más de los
siguientes 4 síntomas principales de psicosis: desorganización conceptual, comportamiento alucinatorio, sospecha y contenido de
pensamiento inusual (derivado de la PANSS)
-La gravedad de la psicosis se evalúa como muy grave (CGI-S de 7)
-Riesgo de suicidio conocido. Los pacientes que hayan mostrado
comportamiento suicida en los últimos 6 meses, como indica un intento real, un intento interrumpido, un intento abortado o actos preparatorios, serán excluidos de participar en el ensayo
-"Resistente al tratamiento" definió síntomas persistentes significativos de esquizofrenia después de dosis adecuadas de dos medicamentos antipsicóticos estándar (de dos clases químicas diferentes, incluido al menos un antipsicótico atípico) después de 6 semanas de tratamiento con cada uno a dosis adecuadas. Se permitirá a los pacientes resistentes al tratamiento que reciban clozapina durante al menos 6 meses si han mostrado una mejoría mínima a juicio del investigador |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| To evaluate the safety, tolerability, and evidence of efficacy of evenamide (30 mg bid) treatment in patients with chronic schizophrenia |
Evaluar la seguridad, tolerabilidad y evidencias de eficacia del
tratamiento con evenamida (30 mg dos veces al día) en pacientes con
esquizofrenia crónica |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
| Tolerability and EEG effects |
| Tolerabilidad y efectos en el EEG |
|
| 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) | 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 28 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| India |
| Mexico |
| Croatia |
| Czechia |
| Germany |
| Hungary |
| Italy |
| Poland |
| United Kingdom |
| Romania |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
| The end of trial will be considered to be the date of completion of any follow-up monitoring and data collection after the last patient completes his/her last visit in the study. |
| Se considerará el final del ensayo como la fecha de finalización de cualquier seguimiento y recogida de datos después de que el último paciente complete su última visita en el estudio |
|
| 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 | 8 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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