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) |
Autismo, Sindrome di Asperger o Disturbo Pervasivo dello Sviluppo non altrimenti specificato (Pervasive Developmental Disorder Not Otherwise Specified, PDD-NOS) |
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E.1.1.1 | Medical condition in easily understood language |
Autism Previously Treated with Memantine |
Autismo precedentemente trattato con memantina |
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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 | 100000004852 |
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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. |
Valutare la sicurezza, la tollerabilità e l’efficacia della terapia con memantina rispetto al placebo in pazienti pediatrici affetti da autismo, sindrome di Asperger, o disturbo pervasivo dello sviluppo non altrimenti specificato (PDD-NOS) precedentemente trattati con dose stabile di memantina utilizzando un paradigma randomizzato dopo la sospensione. |
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E.2.2 | Secondary objectives of the trial |
not applicable |
non applicabile |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion 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. The parents/guardian/LAR must provide written informed consent before the patient's participation in the study.4. Parents who are capable of providing reliable information about the patient's condition, attending all clinic visits with the patient, and overseeing the administration of study drug.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 Italian sufficiently, as well as have parents who are able to speak and understand Italian sufficiently 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.Pazienti che hanno completato almeno 12 settimane di esposizione al farmaco in studio nello studio MEM-MD-91 2.Pazienti che soddisfano i criteri di responsività in due visite consecutive separate da almeno due settimane nello studio MEM-MD-91 (una riduzione di almeno 10 punti nel punteggio totale grezzo di SRS relativo alla Visita 1 di MEM-MD-91) 3. I genitori devono fornire un consenso informato scritto prima della partecipazione del paziente nello studio.4. Genitori in grado di fornire informazioni affidabili sulle condizioni del paziente, in grado di partecipare a tutte le visite in ospedale con il paziente, e in grado di controllare la somministrazione del prodotto in sperimentazione. 5. Avere risultati normali all'esame obiettivo, normali esami di laboratorio, ECG, segni vitali alla Visita 1 del presente studio (ultima visita dello studio MEM-MD-91). Eventuali risultati anomali devono essere considerati non clinicamente significativi dallo sperimentatore e documentati 6. Essere in grado di parlare e capire l'italiano a sufficienza,così come avere dei genitori in grado di parlare e capire l'italiano a sufficienza, per comprendere la natura dello studio e per consentire il completamento di tutte le valutazioni di studio 7. Avere una famiglia che è sufficientemente organizzata e stabile per garantire un adeguato controllo di sicurezza e assistenza continua per le visite ambulatoriali per tutta la durata dello studio 8. Le femmine che hanno 9 anni di età o che hanno avuto inizio delle mestruazioni devono avere un test di gravidanza negativo sulle urine alla Visita 1 |
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E.4 | Principal exclusion criteria |
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. I pazienti con una condizione medica concomitante che potrebbe interferire con la conduzione dello studio, confondendo l'interpretazione dei risultati dello studio, o mettendo in pericolo il benessere del paziente 2. Significativo rischio di suicidio in base al giudizio dello sperimentatore, ABC-I, o, se del caso, come indicato dalla risposta ''sì'' alle domande 4 o 5 nella sezione di ideazione suicidaria di C-SSRS dei bambini (Columbia-Suicide Severity Rating Scale), o qualsiasi comportamento suicidario. 3.I pazienti con evidenza o anamnesi di tumore maligno (diverso dal carcinoma a patologia significativa ematologica, endocrina, cardiovascolare (incluso qualsiasi disturbo del ritmo), neurologica, respiratoria, renale, epatica o gastrointestinale 4. Pazienti di sesso femminile in età fertile che non utilizzano o non vogliono utilizzare un metodo convenzionale di contraccezione approvato dal PI. L'astinenza è un metodo accettabile di contraccezione 5. I pazienti che richiedono un trattamento con farmaci concomitanti vietati 6. Pazienti che, a giudizio del ricercatore, potrebbero non essere adatti per lo studio 7. Dipendente o parente stretto di un dipendente di Forest Laboratories, Inc., o di una delle sue affiliate o partner, o del centro |
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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 above. 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. |
Le valutazioni standard di sicurezza sono condotte per allinearsi con l'obiettivo principale dello studio sopra descritto.La misura di esito primaria in questo studio sarà la percentuale di pazienti che soddisfano il criterio di perdita di risposta terapeutica (Loss of Therapeutic Response, LTR). La LTR è definita come peggioramento (aumento) di almeno 10 punti del punteggio totale grezzo della SRS rispetto al punteggio della Visita 1 (randomizzazione) del presente studio. |
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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 (Fine della settimana 2) Visita 3 (Fine della settimana4) Visita 4 (Fine della settimana 6) Visita 5 (Fine della settimana 8) Visita 6 (Fine della settimana 10) Visita 7 (Fine della settimana 12) |
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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 di controllo 2 della comunicazione dei bambini (CCC-2). Cambiamento dal basale in 10 sottoscale di CCC-2 |
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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 (Fine Settimana 6) Visita 7 (Fine della settimana 12/Visita Finale/Terminazione Anticipata) |
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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 |
Sospensione randomizzata |
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 |
dosaggi differenti dello stesso prodotto |
different dosage of the same product |
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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 | 3 |
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 |
Colombia |
Korea, Republic of |
Mexico |
New Zealand |
Philippines |
Russian Federation |
Singapore |
South Africa |
Taiwan |
Thailand |
Ukraine |
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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 | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 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 |