E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Autism or Asperger's Disorder or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) Previously Treated with Memantine |
Autismo o síndrome de Asperger o Trastorno generalizado del desarrollo no especificado, tratados previamente con Memantine |
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E.1.1.1 | Medical condition in easily understood language |
Autism Previously Treated with Memantine |
Autismo previamente tratado con Memantine. |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Behavioral Disciplines and Activities [F04] |
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 | 10008520 |
E.1.2 | Term | Childhood autism |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003484 |
E.1.2 | Term | Asperger's disorder |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
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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 | 10034739 |
E.1.2 | Term | Pervasive developmental disorder NOS |
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 safety, tolerability, and efficacy of memantine therapy compared with placebo in pediatric patients with autism, Asperger?s Disorder, or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) previously on stable memantine therapy utilizing a randomized withdrawal paradigm. |
Evaluar la seguridad, tolerabilidad y eficacia del tratamiento con memantina en comparación con placebo en pacientes pediátricos con autismo, síndrome de Asperger o trastorno generalizado del desarrollo no especificado (TGD NE) tratados previamente con memantina en dosis estables siguiendo un diseño de retirada aleatorizado. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To be eligible to participate in the study, patients must meet the following criteria: 1. Completed at least 12 weeks of exposure to study drug in lead-in study MEM-MD-91 2. Met responder criterion at two consecutive visits separated by at least two weeks in lead-in study MEM-MD-91 (at least a 10 point reduction in SRS total raw score relative to Visit 1 of MEM-MD-91) 3. Provide written informed assent, when developmentally appropriate, to participate in the study before conduct of any study-specific procedures. The parent/guardian/LAR must provide written informed consent before the patient?s participation in the study. A separate written informed consent for the caregiver must also be obtained before the conduct of any study specific procedures 4. Have a knowledgeable caregiver who is capable of providing reliable information about the patient?s condition, attending all clinic visits with the patient, and overseeing the administration of study drug. Every effort should be made to maintain the same caregiver as used in the lead-in study throughout this study 5. Have normal results from the physical examination, laboratory tests, ECG, and vital signs at Visit 1 of this study (last visit of Study MEM-MD-91). Any abnormal findings must be deemed not clinically significant by the Investigator and documented 6. Be able to speak and understand English sufficiently (or their native language if this can be accommodated by the site), as well as have a caregiver and parent/guardian/LAR who is able to speak and understand English sufficiently (or their native language if this can be accommodated by the site), to comprehend the nature of the study and to allow for the completion of all study assessments 7. Have a family that is sufficiently organized and stable to guarantee adequate safety monitoring and continuous attendance to clinic visits for the duration of the study 8. Females who are 9 years and older or who have had onset of menses must have a negative urine pregnancy test at Visit 1 |
1. Haber completado al menos 12 semanas de exposición al fármaco del estudio en el estudio de preinclusión MEM-MD-91. 2. Haber cumplido el criterio de paciente con respuesta en dos visitas consecutivas separadas por al menos dos semanas en el estudio de preinclusión MEM-MD-91 (una reducción de al menos 10 puntos de la puntuación bruta total SRS con respecto a la visita 1 del estudio MEMMD- 91). 3. Otorgar su asentimiento informado por escrito, en caso de que tenga un desarrollo suficiente, para participar en el estudio antes de realizar ningún procedimiento específico del estudio. El progenitor/tutor/representante legal deberá otorgar su consentimiento informado por escrito antes de la participación del paciente en el estudio. También deberá obtenerse el consentimiento informado por escrito del cuidador antes de realizar ningún procedimiento específico del estudio. 4. Contar con un cuidador informado que sea capaz de facilitar información fiable sobre el estado del paciente, de acudir a todas las visitas al centro con el paciente y de supervisar la administración del fármaco del estudio. Se hará todo lo posible por mantener durante todo el estudio el mismo cuidador que se utilice en el estudio de preinclusión. 5. Tener unos resultados normales en la exploración física, las pruebas analíticas, el ECG y las constantes vitales en la visita 1 de este estudio (última visita del estudio MEM-MD-91). El investigador tendrá que considerar sin importancia clínica los hallazgos anómalos y éstos deberán quedar documentados. 6. Capacidad de hablar y entender suficientemente el inglés (o su idioma cuando esto sea viable en el centro), además de contar con un cuidador y un progenitor/tutor/representante legal capaz de hablar y entender suficientemente el inglés (o su idioma cuando esto sea viable en el centro), para comprender la naturaleza del estudio y permitir la realización de todas las evaluaciones del estudio. 7. Disponer de una familia suficientemente organizada y estable para garantizar una vigilancia adecuada de la seguridad y una asistencia continua a las visitas al centro durante el estudio. 8. Las niñas de 9 años o más de edad o que ya hayan comenzado con la menstruación deberán tener una prueba de embarazo en orina negativa en la visita 1. |
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E.4 | Principal exclusion criteria |
Patients who meet any of the following criteria will not be eligible to participate in the study: 1. Patients with a concurrent medical condition that might interfere with the conduct of the study, confound interpretation of the study results, or endanger the patient?s well being 2. Significant risk of suicidality based on the Investigator?s judgment, ABC-I, or if appropriate, as indicated by a response of ?yes? to questions 4 or 5 in the suicidal ideation section of the Children?s C-SSRS (Columbia-Suicide Severity Rating Scale) or any suicidal behavior 3. Patients with evidence or history of malignancy (other than excised basal cell carcinoma) or any significant hematologic, endocrine, cardiovascular (including any rhythm disorder), neurologic, respiratory, renal, hepatic, or gastrointestinal disease 4. Female patients of child-bearing potential who are not using or not willing to use a conventional method of contraception approved by the PI. Abstinence is an acceptable method of contraception 5. Patients requiring treatment with prohibited concomitant medications 6. Patients who, in the opinion of the Investigator, might not be suitable for the study 7. Employee or immediate relative of an employee of Forest Laboratories, Inc., any of its affiliates or partners, or the study center |
1. Pacientes con trastornos médicos que pudieran interferir en la realización del estudio, confundir la interpretación de los resultados del estudio o poner en peligro el bienestar del paciente. 2. Riesgo significativo de suicidio según el criterio del investigador, la escala ABC-I o, si procede, según lo indicado por una respuesta "sí" a las preguntas 4 o 5 en el apartado de ideación suicida de la escala C-SSRS (Escala de valoración del riesgo de suicidio de la Universidad de Columbia) para niños o cualquier comportamiento suicida. 3. Pacientes con datos o antecedentes de una neoplasia maligna (distinta de un carcinoma basocelular extirpado) o de cualquier enfermedad hematológica, endocrina, cardiovascular (incluidos los trastornos del ritmo), neurológica, respiratoria, renal, hepática o digestiva importante. 4. Niñas en edad fértil que no estén utilizando o no se muestren dispuestas a utilizar un método anticonceptivo convencional aprobado por el IP. La abstinencia será un método anticonceptivo aceptable. 5. Pacientes que requieran tratamiento con medicamentos concomitantes prohibidos (apéndice III). 6. Pacientes que, en opinión del investigador, podrían no ser aptos para el estudio. 7. Empleados y familiares directos de empleados de Forest Laboratories,Inc., de cualquiera de sus filiales o socios o del centro de estudio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Standard safety assessments are being conducted to align with the main objective of the study stated in E.2.1. The primary outcome measure in this study will be the proportion of patients meeting the criterion for Loss of Therapeutic Response (LTR). LTR is defined as worsening (increase) of at least 10 points in the SRS total raw score relative to the score at Visit 1 (randomization) of this study. |
El criterio de valoración principal de este estudio será la proporción de pacientes que cumplan el criterio de pérdida de respuesta terapéutica (PRT) al final del estudio (visita 7/semana 12). La PRT se define como un empeoramiento (aumento) en al menos 10 puntos de la puntuación bruta total SRS con respecto a la puntuación obtenida en la visita 1 (aleatorización) de este estudio. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Visit 2 (End of Week 2) Visit 3 (End of Week 4) Visit 4 (End of Week 6) Visit 5 (End of Week 8) Visit 6 (End of Week 10) Visit 7 (End of Week 12) |
Visita 2 (Final de la semana 2) Visita 3 (Final de la semana 4) Visita 4 (Final de la semana 6) Visita 5 (Final de la semana 8) Visita 6 (Final de la semana10) Visita 7 (Final de la semana12) |
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E.5.2 | Secondary end point(s) |
Children?s Communication Checklist-2 (CCC-2) (Change from baseline in 10 subscales of the CCC?2) |
Lista de comprobación de la comunicación de los niños (CCC-2). Tiempo hasta la primera visita en que un paciente presente PRT después de la aleatorización a memantina o placebo (tiempo hasta la primera PRT). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Visit 4 (End of Week 6) Visit 7 (End of Week 12/Final Visit/Early Termination) |
Visita 4 (Final de la semana 6) Visit 7 (Final de la semana 12/Visita Final/Finalización prematura) |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | 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 | Yes |
E.8.1.7.1 | Other trial design description |
Estudio de retirada |
Randomised withdrawal |
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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 | Yes |
E.8.2.3.1 | Comparator description |
Diferentes dosis del mismo producto (Memantine) |
different dosage of the same product (memantine) |
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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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
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 |
Australia |
Belgium |
Colombia |
Finland |
France |
Germany |
Hungary |
Iceland |
Ireland |
Italy |
Korea, Republic of |
Mexico |
Netherlands |
New Zealand |
Norway |
Philippines |
Poland |
Russian Federation |
Serbia |
Singapore |
Slovakia |
South Africa |
Spain |
Sweden |
Taiwan |
Thailand |
Ukraine |
United Kingdom |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial months | 10 |