| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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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 | 10064104 |
| E.1.2 | Term | ADHD |
| 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 |
| The primary objective of this study is to evaluate the long-term maintenance of efficacy of SPD503 in children and adolescents (6-17 years) with attention-deficit/hyperactivity disorder (ADHD) who respond to an initial openlabel, short-term treatment with SPD503. |
| L’obiettivo primario di questo studio e' quello di valutare il mantenimento a lungo termine dell’efficacia di SPD503 in bambini e adolescenti (6-17 anni) con disordine di iperattivita'/deficit d’attenzione (ADHD) che rispondono a un trattamento iniziale a breve termine in aperto con SPD503. |
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| E.2.2 | Secondary objectives of the trial |
| 1-To assess the long-term efficacy of SPD503 using the clinician-dministered Attention-deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) total score.2-To assess the long-term efficacy of SPD503 using the clinician-administered Global Impressions- Severity of Illness Scale (CGI-S).3-To assess the efficacy of SPD503 using the clinician-administered Clinical Global Impressions-Improvement Scale (CGI-I).4-To evaluate efficacy on ADHD functional outcomes as measured by the Weiss Functional Impairment Rating Scale-Parent (WFIRS-P).5-To assess the impact of treatment on the perception of health state preferences using the Health Utilities Index-Mark 2 and Mark 3 (HUI-2/3).6-To evaluate the long-term safety of SPD503 based on treatment-emergent adverse events (TEAEs), specific evaluation of blood pressure and pulse, clinical laboratory tests, electrocardiogram (ECG) results, and results from the Columbia-Suicide Severity Rating Scale (C-SSRS). |
| 1-Valutare l’efficacia a lungo termine di SPD503 mediante il punteggio totale della ADHD-RS-IV somministrata dal medico.2-Valutare l’efficacia a lungo termine di SPD503 mediante la CGI-S somministrata dal medico.3-Valutare l’efficacia di SPD503 mediante la Clinical Global Impressions -improvement Scale (CGI-I)somministrata dal medico.4-Valutare l’efficacia in termini di esiti funzionali dell’ADHD misurati con la Weiss Functional Impairment Rating Scale-Parent (WFIRS-P).5-Valutare l’impatto del trattamento sulla percezione delle preferenze sullo stato di salute mediante Health Utilities Index - Mark 2 e Mark 3 (HUI-2/3).6-Valutare la sicurezza a lungo termine di SPD503 in base agli eventi avversi emersi durante il trattamento (TEAE), alla valutazione specifica di pressione arteriosa e polso, ai test clinici di laboratorio, ai risultati degli elettrocardiogrammi (ECG) e ai risultati della Columbia-Suicide Severity Rating Scale (C-SSRS). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| 1. Male or female, aged 6-17 years at the time of consent/assent at Screening/Visit 1. 2. Subject meets Diagnostic and Statistical Manual of Mental Disorders, 4th ed.-Text Revision (DSM-IV-TR ) criteria for a primary diagnosis of ADHD, combined sub-type, hyperactive/impulsive sub-type, or inattentive sub-type based on a detailed psychiatric evaluation using the Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime version (K-SADS-PL). 3. Subject has a minimum ADHD-RS-IV total score of 32 at Enrolment/Visit 2. 4. Subject has a minimum CGI-S score of 4 at Enrolment/Visit 2. 5. Subject is able to swallow intact tablets. |
| 1. Maschio o femmina di 6-17 anni di eta' al momento del consenso/assenso allo Screening/Visita 1. 2. Il soggetto deve soddisfare i criteri di Diagnostic and Statistical Manual of Mental Disorders, 4a ed. -Text Revision (DSM-IV-TR ) per una diagnosi primaria di ADHD, sottotipo combinato, sottotipo iperattivo/impulsivo o sottotipo disattento in base a una valutazione psichiatrica dettagliata mediante Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime version (K-SADS-PL). 3. Punteggio totale ADHD-RS-IV minimo pari a 32 ad Arruolamento/Visita 2. 4. Punteggio CGI-S minimo pari a 4 ad Arruolamento/Visita 2. 5. Il soggetto deve essere in grado di inghiottire compresse intere. |
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| E.4 | Principal exclusion criteria |
| 1. Subject has a current, controlled (requiring a prohibited medication or behavioural modification program) or uncontrolled, co-morbid psychiatric diagnosis, except Oppositional Defiant Disorder (ODD), including any severe comorbid Axis II disorders or severe Axis I disorders such as Post Traumatic Stress Disorder, bipolar illness, psychosis, pervasive developmental disorder, obsessive-compulsive disorder, substance abuse disorder, or other symptomatic manifestations or lifetime history of bipolar illness, psychosis, or conduct disorder that, in the opinion of the Investigator, contraindicate SPD503 treatment or confound efficacy or safety assessments. 2. Subject has a known history or presence of structural cardiac abnormalities, serious heart rhythm abnormalities, syncope, cardiac conduction problems (e.g., clinically significant heart block), exercise-related cardiac events including syncope and pre-syncope, or clinically significant bradycardia. 3. Subject with orthostatic hypotension or a known history of controlled or uncontrolled hypertension. 4. Current use of any prohibited medication or other medications, including herbal supplements, that affect blood pressure (BP) or heart rate or that have central nervous system (CNS) effects or affect cognitive performance, such as sedating antihistamines and decongestant sympathomimetics (inhaled bronchodilators are permitted) or a history of chronic use of sedating medications (i.e., antihistamines) in violation of the protocol specified washout criteria at Enrolment/Visit 2. 5. Subject is significantly overweight based on Centre for Disease Control and Prevention Body Mass Index (BMI)-for-age gender specific charts. Significantly overweight is defined as a BMI >95th percentile. 6. Children aged 6-12 years with a body weight of <25.0kg or adolescents aged 13-17 years with a body weight of <34.0kg or >91.0kg at Screening/Visit 1. 7. Subject has a history of alcohol or other substance abuse or dependence, as defined by DSM-IV-TR (with the exception of nicotine) within the last 6 months. 8. Subject is currently considered a suicide risk in the opinion of the Investigator, has previously made a suicide attempt, or has a prior history of, or is currently demonstrating active suicidal ideation. Subjects with intermittent passive suicidal ideation are not necessarily excluded based on the assessment of the Investigator (see protocol for additional guidance). 9. History of failure to respond to an adequate trial of an α2-agonist for the treatment of ADHD (consisting of an appropriate dose and adequate duration of therapy in the opinion of the Investigator). |
| 1. Il soggetto presenta una diagnosi psichiatrica comorbile in atto, controllata (che necessita di un farmaco vietato o di un programma di modifica comportamentale) o incontrollata, a eccezione del disordine oppositivo provocatorio (ODD), tra cui disordini comorbili gravi dell’Asse II o disordini gravi dell’Asse I, come disordine da stress post-traumatico, malattia bipolare, psicosi, disordine pervasivo dello sviluppo,disordine ossessivo - compulsivo, disordine da abuso di sostanze o altre manifestazioni sintomatiche correnti o pregresse di malattia bipolare, psicosi o disordine della condotta che, in base al giudizio dello Sperimentatore, controindicano il trattamento con SPD503 o interferiscono con le valutazioni di efficacia o sicurezza. 2- Il soggetto ha una storia nota o presenza di anomalie cardiache strutturali, anomalie gravi del ritmo cardiaco, sincope, problemi di conduzione cardiaca (ad es. blocco cardiaco clinicamente significativo), eventi cardiaci correlati all’esercizio fisico, come sincope e pre-sincope, o bradicardia clinicamente significativa. 3- Soggetto con ipotensione ortostatica o storia nota di ipertensione controllata o incontrollata.4- Uso attuale di farmaci vietati o altri farmaci, compresi gli integratori erboristici, che influiscono sulla pressione arteriosa (BP) o la frequenza cardiaca, o che hanno effetti sul sistema nervoso centrale (SNC) o influiscono sulla performance cognitiva, come sedativi antistaminici e decongestionanti simpatico-mimetici (i broncodilatatori per inalazione sono ammessi) o storia di uso cronico di sedativi (antistaminici) in violazione dei criteri di wash-out specificato dal protocollo all’Arruolamento/Visita 2. 5- Soggetto in sovrappeso significativo in base all’indice di massa corporea (BMI) per eta' secondo le tabelle specifiche per sesso del Centre for Disease Control and Prevention. Il sovrappeso significativo e' definito come BMI > 95° percentile. 6- Bambini di 6-12 anni con peso corporeo < 25,0 kg o adolescenti di 13-17 anni con peso corporeo < 34,0 kg o > 91,0 kg allo Screening/Visita 1. 7- Il soggetto ha una storia di abuso o dipendenza da alcool o altre sostanze, secondo la definizione di DSM-IV-TR (a eccezione della nicotina), negli ultimi 6 mesi. 8- Il soggetto e' attualmente considerato a rischio di suicidio secondo il giudizio dello Sperimentatore, ha tentato il suicidio in precedenza o presenta una storia pregressa o corrente di ideazione suicidaria attiva. I soggetti con ideazione suicidaria passiva intermittente non sono necessariamente esclusi in base alla valutazione dello Sperimentatore (si veda il protocollo per ulteriori indicazioni). 9- Storia di mancata risposta a un trattamento adeguato dell’ADHD con un a2-agonista (basato su una dose appropriata e un’opportuna durata della terapia a giudizio dello Sperimentatore). |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy outcome for each subject is treatment failure during the double-blind randomisedwithdrawal phase (Phase 2), defined as a >/=50% increase (worsening) in ADHD RS-IV total score at 2 consecutive Phase 2 visits (Visits 14-23/ Early Termination) relative to Visit 13 and a >/=2 point increase in CGIS score relative to CGI-S at Visit 13 at the corresponding Phase 2 visits. |
| L'esito primario di efficacia per ogni soggetto e' il fallimento della terapia durante il ritiro in doppio cieco randomizzato (fase 2), definito come un aumento > / = al 50% (peggioramento) nel total score del punteggio ADHD RS-IV per 2 visite consecutive di fase 2 (visita 14-23 / Early Termination) rispetto alla visita 13 e a un incremento > / = 2 nello score di CGI-S relativo al CGI-S della vista 13 e alla corrispondente visita di fase 2 |
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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 | No |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
| fase di ottomizzazione/mantenimento dose in aperto, seguita da ritiro randomizzato |
|
| 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 | 11 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 30 |
| 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 | 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
|
| la fine dello studio e' definita come visita di follow up per la sicurezza ( 7 giorni dopo l'ultima dose di farmaco, per l'utimo paziente) |
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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 | 26 |
| 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 | 26 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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