E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Fragile X Syndrome (FXS) |
Síndrome de X Frágil |
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E.1.1.1 | Medical condition in easily understood language |
FXS is a genetic condition caused by a change in the FMR1 gene. A defect in this gene causes your body to produce too little or none of a protein that is needed for normal brain development. |
Síndrome X Frágil:condición genética por cambio en gen FMR1. Un defecto en este gen provoca que el cuerpo produzca muy poca/ninguna cantidad de proteina necesaria para dllo. normal cerebro. |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025463 |
E.1.2 | Term | Major depressive disorder, single episode |
E.1.2 | System Organ Class | 10037175 - Psychiatric 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 evaluate the efficacy of 12-week treatment with RO4917523 in patients with Fragile X Syndrome (FXS) as measured by the ADAMS social avoidance factor. ? To evaluate the safety and tolerability of 12-week treatment with RO4917523 in patients with FXS |
Evaluar la eficacia de un tratamiento de 12 semanas de duración con RO4917523 en pacientes con SXF medida según el factor de evitación social de la Escala de Ansiedad, Depresión y Estado de Ánimo (ADAMS, por sus siglas en ingles: Anxiety Depression and Mood Scale). ? Evaluar la seguridad y la tolerabilidad de un tratamiento de 12 semanas de duración con RO4917523 en pacientes con SXF. |
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E.2.2 | Secondary objectives of the trial |
? Change from baseline in symptoms as measured by the: Aberrant Behaviour Checklist (ABC) total, ABC factor scores, Anxiety Depression and Mood Scale (ADAMS) total, ADAMS factor scores, and Social Responsiveness Scale (SRS) ? Change from baseline in cognitive function as measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) ? Clinical Global Impression-Improvement (CGI-I) and change from baseline in the Clinical Global Impression-Severity (CGI-S) ? Clinical response (at least 25% improvement in the ABC total score and a CGI-I score of 1 or 2) ? Change in the caregiver-identified most troubling symptom as measured by the Visual Analogue Scale (VAS) ? Change from baseline in adaptive behaviour skills as measured by the Vineland Adaptive Behavior Scale (VABS-II) |
? Cambio respecto a síntomas iniciales medidos según: puntuación total según la Lista de Comprobación de Comportamientos Aberrantes, puntuaciones de factores ABC, puntuación total en la escala ADAMS, puntuaciones de factores de escala ADAMS y la Escala de Respuesta Social (SRS) ? Cambio respecto a valores iniciales en función cognitiva, medida según Batería Repetible para la Evaluación del Estado Neuropsicológico (RBANS) ? Impresión Clínica Global-Mejoría (CGI-I) y cambio respecto de los valores iniciales de Impresión Clínica Global Gravedad de la Enfermedad (CGI-S) ? Respuesta clínica (mejoría de al menos un 25 % en la puntuación total ABC y puntuación de 1 o 2 en CGI-I) ? Cambio en síntomas más problemáticos identificados por el cuidador, medidos según Escala Visual Analógica (EVA) ? Cambio en las habilidades de comportamiento adaptativo respecto a valores iniciales, medidas según la Escala de Conducta Adaptativa de Vineland-II (VABS-II) |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Sampling Substudy for the Roche clinical Repository:to identify biomarkers NP27936D - 16 April 2012. Same protocol as main study |
Subestudio de Muestras para el banco de muestras clínicas de Roche: para identificar biomarcadores NP27936D - 16 Abril 2012 Mismo protocolo que el estudio principal |
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E.3 | Principal inclusion criteria |
? Adults and adolescents (16 to 50) ? CGI-S of 3 (mildly ill) or more ? ABC total score of 20 or more ? Diagnosis of FXS with a confirmed FMR1 full mutation |
? Adultos y adolescentes (de 16 a 50) ? CGI-S de 3 (moderadamente enfermos) o más ? Puntuación total de ABC de 20 o más ? Diagnóstico de SXF con mutación completa del FMR1 confirmada |
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E.4 | Principal exclusion criteria |
? Have previously received treatment with another mGlu5 receptor antagonist within 18 months or RO4917523 ? Enrollment/participation in any interventional study (clinical trial) involving an investigational drug (unapproved) or non-drug treatment within the prior 3 months or 5 times the half-life (whichever is longer) ? Any uncontrolled, unstable clinically significant psychiatric condition other than FXS that may interfere with interpretation of safety and efficacy evaluations (e.g. Attention Deficit Hyperactivity Disorder (ADHD)) ? Current symptoms or presumption of psychosis or euphoria, history of catatonia, hallucinations or delusional thoughts ? History of suicidal behaviour or otherwise considered a high suicidal risk by the investigator |
? Ha recibido un tratamiento previo con otro antagonista de receptor del mGlu5 hace menos de 18 meses, o con RO4917523 ? Inclusión/participación en cualquier estudio de intervención (ensayo clínico) sobre un fármaco experimental (no aprobado) o un tratamiento sin fármacos durante los 3 meses anteriores o 5 veces la semivida (el período de mayor duración) ? Cualquier trastorno psiquiátrico no controlado o inestable y clínicamente significativo, distinto del SXF, que pudiera interferir con la interpretación de las evaluaciones de la seguridad y la eficacia (Trastorno de Deficit de Atención e Hiperactividad) ? Síntomas manifiestos o presunción de psicosis o euforia, historial de catatonia, alucinaciones o pensamientos delirantes ? Historial de conducta suicida o cualquier otro indicio que el investigador considere con alto riesgo de suicidio |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in the ADAMS social avoidance factor from baseline to end of treatment |
Cambio en el factor de evitación social de la Escala de Ansiedad, Depresión y Estado de Ánimo (ADAMS) desde el inicio hasta el final del tratamiento |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Change from baseline to end of treatment (12 weeks) |
Cambio desde el inicio hasta el final del tratamiento (12 semanas) |
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E.5.2 | Secondary end point(s) |
? Change from baseline in symptoms as measured by the ABC and ADAMS (total and factor scores), and the SRS ? Change from baseline in cognitive function as measured by the RBANS ? CGI-I and change from baseline in the CGI-S ? Clinical response (at least 25% improvement in the ABC total score and a CGI-I score of 1 or 2) ? Change in the caregiver-identified most troubling symptom as measured by the VAS ? Change from baseline in adaptive behavior skills as measured by the VABS-II ? To investigate the pharmacokinetics and exposure response relationship of RO4917523 in patients with FXS using a population analysis approach. |
? Cambio respecto a síntomas iniciales medidos por ABC y ADAMS (puntuaciones de factores y total) y la Escala (SRS) ? Cambio respecto a valores iniciales en función cognitiva, medida según RBANS ? CGI-I y cambio respecto de los valores iniciales de CGI-S ? Respuesta clínica (mejoría de al menos un 25 % en la puntuación total ABC y puntuación de 1 o 2 en CGI-I) ? Cambio en síntomas más problemáticos identificados por el cuidador, medidos según EVA ? Cambio en las habilidades de comportamiento adaptativo respecto a valores iniciales, medidas según VABS-II ? Investigar la farmacocinética y la relación exposición-respuesta del fármaco RO4917523 en pacientes con SXF utilizando un método de análisis de población |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Change from baseline to end of treatment (12 weeks) |
Cambio desde el inicio hasta el final del tratamiento (12 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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Patient Reported Outcomes, Psychometric testing of assessment scales for use in FXS |
Resultados comunicados del Paciente, ensayos psicométricos de las escalas de evaluación para su uso en Síndrome de X frágil |
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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) | No |
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 | 3 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 |
Canada |
Chile |
France |
Mexico |
Peru |
Spain |
Sweden |
United Kingdom |
United States |
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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
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |