| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Attention Deficit/Hyperactivity Disorder ADHD |
| Deficit di attenzione/disordine d'iperattivita' |
|
| 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 | 10064104 |
| E.1.2 | Term | ADHD |
| E.1.2 | System Organ Class | 100000004873 |
|
| 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 |
| The primary objective of this study is to evaluate the efficacy of LDX administered with one daily dose in the morning (30, 50 ande 70 mg/dayie) versus placebo during 7 weeks . The study will enroll children and adolescents (6−17 years included of age ) with diagnosis of moderately symptomatic ADHD moderately symptomatic . The primary measure of the efficacy will be the clinician-administered ADHD rating scale IV (ADHD-RS-IV) |
| L`obiettivo primario di questo studio e` quello di valutare l`efficacia di LDX somministrato una volta al giorno al mattino (30, 50 e 70 mg/die) rispetto a placebo per 7 settimane. Lo studio riguardera` bambini e adolescenti (di eta` compresa tra 6-17 anni inclusi) con diagnosi di ADHD moderatamente sintomatico. La misura primaria dell`efficacia sara` la scala di valutazione dell`ADHD somministrata dal medico (ADHD-RS-IV). |
|
| E.2.2 | Secondary objectives of the trial |
| The key secondary objective of this study is to assess the efficacy of LDX compared to placebo using a global clinical measure of improvement, the Clinical Global Impressions ` Global Improvement (CGI-I). The other secondary objectives of this study are listed below: 1. To assess the duration of therapeutic response to LDX compared to placebo using the Conners` Parent Rating Scale ` Revised (CPRS-R) performed in the morning (around 10:00AM), afternoon (around 2:00PM), and evening (around 6:00PM). 2. To assess the impact of LDX compared to placebo on the perception of health state preferences and quality of life (QoL) using the Health Utilities Index ` Mark 2 (HUI-2) and the Child Health and Illness Profile, Child Edition: Parent Report Form (CHIP CE:PRF), respectively. 3. To assess the relationship of change in the core symptoms of ADHD with the changes in functional outcomes, as assessed by the Weiss Functional Impairment Rating Scale ` Parent (WFIRS-P), in subjects treated with |
| valut l`eff di LDX risp a pl mediante la misura clin glob del miglioramento(CGI-I).1.Det.la durata della risp terapeutica a LDX risp a pl med scala Conners Parent Rating Scale-Revised applicata al mattino, pomeriggio e sera2imp di LDX risp a pl sulla percez delle pref relative allo stato di salute e alla QoL con indice Health Utilities Index-Mark 2e lo strum Child Health and Illness Profile-Child Edition:Parent Report Form3.rapporto tra le Variaz dei sintomi principali di ADHD e le Variaz degli esiti funzionali,in base alla scala Weiss Functional Impairment Rating Scale Parent,nei sogg tratt con LDX rispetto a pl.4.sicur.di LDX in base alla comparsa di EA emersi durante il tratt,alla valut spec di pressione arteriosa e polso,ai risultati elettrocardiogr,agli esiti dei test clin dilab e ai ris degli es ob5.Monit la sicur.dei sogg sulla base delle risp a Brief Psychiatric Rating Scale for Children e a Columbia-Suicide Severity Rating Scale6.Valut la sicur.e l`eff di CONCERTA risp a pl |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| 1. Subject s parent or legally authorised representative (LAR) shall sign the informed consent, and documentation of assent (if applicable) is required by the subject indicating that the subject is aware of the investigational nature of the study and of the required procedures and restrictions, in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6 and applicable regulations before performing any study-related procedures. 2. Subject and parent/LAR must be willing and able to comply with all the tests and requirements defined in this protocol, including supervision of morning dosing. Specifically, the parent/LAR must be available upon awakening, at approximately 7:00AM, to dispense the dose of study drug for the duration of the study. 3. Subject is a male or female aged 6-17 years inclusive at the time of consent. 4. Subject must meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision (DSM IV TR) criteria for a primary diagnosis of ADHD based on a detailed psychiatric evaluation. 5. Subject must have a Baseline ADHD-RS-IV total score 28. 6. Female subjects of childbearing potential (FOCP), must have a negative serum beta human chorionic gonadotropin (HCG) pregnancy test at Screening and a negative urine pregnancy test at Baseline and must agree to comply with any applicable contraceptive requirements of the protocol. 7. Subject has blood pressure measurements within the 95th percentile for age, gender, and height at Screening and Baseline. 8. Subject has an age-appropriate intellectual level, as deemed by the study investigator. 9. Subject is able to swallow a capsule. |
| 1. Prima di eseguire qualsiasi procedura dello studio, un genitore o un rappresentante legalmente autorizzato del soggetto (LAR) dovra` firmare il consenso informato e una documentazione dell assenso (se necessario) dovra` attestare che il soggetto e` consapevole della natura sperimentale dello studio e delle procedure e limitazioni previste, in conformita` alla Linea Guida E6 di International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) e ai regolamenti apllicabili. 2. Il soggetto e il genitore/LAR devono essere disposti a e in grado di conformarsi a tutti i requisiti e i test previsti dal protocollo, inclusa la supervisione del dosaggio mattutino. Nello specifico, il genitore/LAR (se necessario) devono essere disponibili al momento del risveglio, all incirca alle 7,00 del mattino, per somministrare la dose di farmaco in studio per tutta la durata della ricerca 3. Al momento del consenso il soggetto di sesso maschile o femminile deve avere un eta` compresa tra 6-17 anni inclusi. 4. Il soggetto deve soddisfare i criteri di Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Text Revision (DSM-IV-TR) per una diagnosi primaria di ADHD basata su una valutazione psichiatrica dettagliata 5. Il soggetto deve avere un punteggio totale basale di ADHD-RS-IV  28. 6. Le pazienti fertili in grado di procreare (FOCP) devono presentare un test di gravidanza sierico della gonadotropina corionica umana beta (HCG) negativo allo Screening e un test di gravidanza urinario negativo al basale e devono accettare di conformarsi ai requisiti applicabili previsti dal protocollo in materia di contraccezione. 7. Il soggetto presenta misurazioni della pressione sanguigna comprese nel 95° percentile per eta`, sesso e altezza allo Screening e al Basale 8. In base al giudizio dello sperimentatore dello studio, il soggetto e` in grado di agire con un livello intellettuale adeguato all eta`. 9. Il soggetto e` in grado di ingerire una capsula. |
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| E.4 | Principal exclusion criteria |
| 1. Subject has failed to respond to more than one adequate regimen (dose and duration) of stimulant treatment. One regimen must have been a long-acting formulation. 2. Subject has a current, controlled (requiring a restricted treatment) or uncontrolled, comorbid psychiatric diagnosis with significant symptoms such as any severe comorbid Axis II disorder or severe Axis I disorder (such as Post Traumatic Stress Disorder, psychosis, bipolar illness, pervasive developmental disorder, severe obsessive compulsive disorder, anorexia nervosa, severe depressive or severe anxiety disorder) or other symptomatic manifestations, such as agitation states, marked anxiety, or tension that, in the opinion of the examining physician, contraindicate treatment with LDX or CONCERTA XL or confound efficacy or safety assessments. Comorbid psychiatric diagnoses will be established with the Screening interview of the Kiddie-SADS-Present and Lifetime Diagnostic Interview (K SADS-PL) and additional modules if required by the results of the initial interview. Subjects may continue participating in behavioural therapy during this study as long in the case of being included in the program since at least 1 month at the time of the Baseline Visit. 3. Subject has a conduct disorder. Oppositional Defiant Disorder is not an exclusion cause . 4. Subject has a concomitant chronic or acute illness (such as severe allergic rhinitis or an infectious process requiring antibiotics), disability, or other condition that might interfere with the results of safety assessments conducted in the study or that might increase risks for the subject. Similarly, the subject will be excluded if he or she has any additional condition that, in the Investigator s opinion, might prohibit the subject from completing the study or would not be convenient for the subject. Additional conditions include any significant disease or unstable medical condition that might lead to difficulties in complying with the protocol. Mild, stable asthma is not an exclusion cause . 5. Subject is currently considered at suicide risk, has previously made a suicide attempt or has a prior history of, or has currently, active suicidal intentions . 6. Subject is female and is pregnant or lactating. 7. Subject has glaucoma. 8. Subject weight is below 22.7kg (50lbs). 9. Subject is significantly overweight (defined as a BMI >97th percentile) based on Centre for Disease Control and Prevention Body Mass Index (BMI)-for-age gender specific charts at Screening. 10. Subject is positive at urine drug Screening analysis (with the exception of subject s current ADHD treatment). 11. Subject has current abnormal thyroid function, defined as abnormal thyroid stimulating hormone (TSH) at Screening. Treatment with a stable dose of thyroid drug for at least 3 months is permitted. 12. Subject has clinically significant laboratory or ECG abnormalities at Screening and/or Baseline. 13. Subject has a documented allergy, hypersensitivity, or intolerance to amphetamine or methylphenidate. 14. Subject has a documented allergy, hypersensitivity, or intolerance to any excipients in the investigational or comparison product. 15. Subject has a recent history (within the past 6 months) of suspected substance abuse or dependence disorder (excluding nicotine) in compliance with DSM-IV-TR criteria.16. Subject has a history of seizures (other than infantile febrile seizures), a chronic or current tic disorder, or acurrent diagnosis and/or a known family history of Tourette s Disorder. Subject has history of tics |
| 1.Il soggetto non ha risposto a piu` di un regime adeguato (dose e durata) di CONCERTA 2. Il soggetto presenta una diagnosi psichiatrica comorbile in atto, controllata (che necessita di una terapia limitata) o incontrollata con sintomi significativi quali un qualsiasi disordine comorbile grave dell Asse II o un disordine grave dell Asse I (come disordine da stress post-traumatico, psicosi, malattia bipolare, disordine pervasivo dello sviluppo, disordine ossessivo-compulsivo grave, anoressia nervosa, disordine da depressione grave o ansia grave) o altre manifestazioni sintomatiche quali stati di agitazione, ansia marcata o tensione che, in base al giudizio del medico esaminante, risultano controindicate per il trattamento con LDX o CONCERTA XL o interferiscono con le valutazioni di efficacia o sicurezza. Le diagnosi psichiatriche comorbili saranno formulate allo Screening mediante l intervista Kiddie-SADS-Present and Lifetime Diagnostic Interview (K-SADS-PL) e con ulteriori moduli se richiesto dai risultati dell intervista iniziale. I soggetti potranno continuare a partecipare a programmi di modifica del comportamento durante lo studio nel caso in cui fossero gia` inclusi in tali programmi da almeno 1 mese all epoca della Visita Basale. 3. Il soggetto presenta un disordine della condotta. Il disordine oppositivo provocatorio non e` motivo d esclusione. 4. Il soggetto presenta una malattia concomitante cronica o acuta (quale la rinite allergica grave o un processo infettivo che necessitano di antibiotici), una disabilita`, o un altra condizione che potrebbero interferire con i risultati delle valutazioni di sicurezza condotte nello studio o che potrebbero aumentare i rischi. Similmente, il soggetto sara` escluso se presenta qualsiasi condizione aggiuntiva, che in base al giudizio dello sperimentatore, potrebbe impedire il completamento della ricerca o che potrebbe risultare non vantaggiosa. Cio` potrebbe includere qualsiasi malattia significativa o condizione medica instabile che potrebbe creare delle difficolta` in termini di rispetto del protocollo. Un asma lieve e stabile non e` motivo di esclusione. 5. Il soggetto e` considerato a rischio di suicidio, ha gia` tentato il suicidio in precedenza o ha una storia passata o in atto di intenzioni suicide. 6. Soggetto di sesso femminile in gravidanza o che allatta al seno. 7. Il soggetto e` affetto da glaucoma. 8. Il soggetto pesa meno di 22,7kg (50 libbre). 9. Il soggetto presenta allo Screening un significativo sovrappeso in base all Indice di Massa Corporea (BMI-per-eta` >97° percentile) secondo le tabelle BMI specifiche per eta` e sesso di Center for Disease Control and Prevention 10. Il soggetto risulta essere positivo al test delle urine per sostanze stupefacenti allo Screening (fatta eccezione per la terapia di ADHD in atto). 11. Il soggetto ha una funzionalita` tiroidea anomala in atto, definita come anomalia dell ormone stimolante la tiroide (TSH) e tiroxina ( T4) allo Screening. E` consentito il trattamento con una dose stabile di farmaco tiroideo per almeno 3 mesi. 12. Il soggetto presenta anomalie di laboratorio o di ECG clinicamente significative allo Screening e/o al Basale 13. Il soggetto ha un allergia documentata, ipersensibilita` o intolleranza all amfetamina o al metilfenidato. 14. Il soggetto ha un allergia documentata, ipersensibilita` o intolleranza a uno degli eccipienti del prodotto sperimentale o di confronto. 15. Il soggetto ha una storia recente (negli ultimi 6 mesi) di sospetto abuso di sostanze o disordine da dipendenza (esclusa la nicotina) in conformita` ai criteri DSM-IV-TR. 16.Il soggetto ha una storia di attacchi epilettici (fatta eccezione per le convulsioni febbrili infantili), un disordine da tic cronico o in corso, o una diagnosi corrente o una storia familiare nota di Sindrome di Tourette. Il soggetto ha una storia di ti |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint for this study is defined as the change from Baseline score of the ADHD RS IV total score at Endpoint, defined as the last on-therapy post-randomisation treatment week (up to Visit 7/ET) at which a valid ADHD-RS-IV total score is observed. |
| L`endpoint primario per questo studio e` definito come la variazione rispetto al punteggio basale del punteggio totale ADHD RS IV all Endpoint, definito come l ultima settimana di trattamento post-randomizzazione (fino alla Visita 7/ET) in cui viene osservato un punteggio totale valido di ADHD RS IV. |
|
| 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 | Yes |
| 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) | 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 | 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) | Yes |
| 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 | 80 |
| 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
| |
| 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 | 25 |
| 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 | 25 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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