| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| 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 |
|
| 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 safety of SPD489 administered as a daily morning dose (30, 50, and 70mg) in the treatment of children and adolescents (6-17 years of age inclusive at the time of consent in this study or a previous SPD489 study (SPD489-317, SPD489-325, or SPD489-326) diagnosed with moderately to severely symptomatic ADHD. |
| L’obiettivo primario di questo studio e' quello di valutare la sicurezza a lungo termine di SPD489 somministrato con una dose giornaliera mattutina (30, 50 e 70mg) per il trattamento di bambini e adolescenti (con 6-17 anni d’eta' compiuti al momento del rilascio del consenso a questo studio o a uno studio SPD489 precedente [SPD489-317, SPD489-325, or SPD489-326]) con diagnosi di ADHD da moderatamente a gravemente sintomatica. |
|
| E.2.2 | Secondary objectives of the trial |
1. To assess the long-term efficacy of SPD489 using the clinician-administered ADHD-rating scale-IV (ADHD RS IV) total score and hyperactivity/impulsivity and inattentiveness subscale scores.
2. To assess the long-term efficacy of SPD489 using global clinical measures of severity and improvement as measured by the Clinical Global Impressions – Severity of Illness (CGI-S) and Clinical Global Impressions – Global Improvement (CGI-I). |
1. Determinare l’efficacia a lungo termine di SPD489 utilizzando il punteggio totale della Scala IV di Classificazione di ADHD somministrata dal medico (ADHD RS IV) e i punteggi delle sotto-scale iperattivita'/impulsivita' e disattenzione.
2. Accertare l’efficacia a lungo termine di SPD489 utilizzando le misure cliniche globali di gravita' e miglioramento misurate in base a Impressioni Cliniche Globali – Gravita' della Malattia (CGI-S) e Impressioni Cliniche Globali - Miglioramento Globale (CGI-I). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
For subjects who participated in another SPD489 study (SPD489-317, SPD489-325 and/or SPD489 326):
1. Subject is a male or female aged 6-17 years inclusive at the time of consent for the previous SPD489 study.
2. For sites where Study SPD489-326 (12-month open-label or randomised withdrawal design) was not available at the time of subject’s final visit in Study SPD489-325, subject satisfied all entry criteria for the antecedent study (SPD489 325), completed a minimum of 4 weeks of double-blind treatment, reached Visit 4, and completed the 1 week post-treatment washout in Study SPD489-325.
3. For sites where Study SPD489-326 (12-month open-label design) was available at the time of subject’s final visit in Study SPD489-325, subject satisfied all entry criteria and was enrolled in the antecedent study (SPD489 326).
4. For sites where Study SPD489-326 (randomised withdrawal design) was available at the time of subject’s final visit in Study SPD489-325, subject satisfied all entry criteria for the antecedent study (SPD489-326), and either completed the post-treatment follow-up call/visit or was withdrawn from the study during the randomisation withdrawal period due to meeting relapse criteria in the antecedent study (SPD489 326).
5. Subject participated in SPD489-317, completed 9 weeks of treatment, and completed the 1 week post-treatment safety follow-up visit.
6. Subject participated in a prior SPD489 study (SPD489-317, SPD489-325, or SPD489-326) and had a gap in participation (eg, >7 days) between exiting the previous study and entering this study The subject’s ADHD-RS-IV total score at Study SPD489-404 Baseline (Visit 0) must be ≥28.
For subjects who have not participated in another SPD489 study:
7. Subject is a male or female aged 6-17 years inclusive at the time of consent.
8. 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.
9. Subject has a Baseline (Visit 0) ADHD-RS-IV total score ≥28.
For all subjects:
10. Subject, who is female of childbearing potential (FOCP), must have a negative serum beta Human Chorionic Gonadotropin (HCG) pregnancy test at Screening (Visit –1) and a negative urine pregnancy test at Baseline (Visit 0), be non-lactating, and agree to comply with any applicable contraceptive requirements of the protocol.
11. Subject’s parent or legally authorised representative (LAR) must provide signature of informed consent, and there must be documentation of assent (if applicable) by the subject indicating that the subject is aware of the investigational nature of the study and the required procedures and restrictions in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6 and applicable regulations, before completing any study-related procedures.
12. Subject and parent/LAR are willing and able to comply with all the testing and requirements defined in this protocol, including oversight of morning dosing. Specifically, the parent/LAR must be available upon awakening, at approximately 7:00AM, to dispense the dose of Investigational Product for the duration of the study.
13. Subject has blood pressure measurements within the 95th percentile for age, sex, and height at Screening (Visit 1) and Baseline (Visit 0).
14. Subject is functioning at an age-appropriate level intellectually, as deemed by the study Investigator.
15. Subject is able to swallow a capsule. |
1. Soggetto di sesso maschile o femminile di eta' compresa tra 6-17 anni compiuti all’epoca del rilascio del consenso allo studio SPD489 precedente.
2. Per i centri in cui lo Studio SPD489-326 (disegno 12-mesi, in aperto o con ritiro randomizzato) non era disponibile al momento della visita finale del soggetto nello Studio SPD489-325, il soggetto deve aver soddisfatto tutti i criteri di ingresso per lo studio antecedente (SPD489 325), completato un minimo di 4 settimane di trattamento in doppio cieco, raggiunto la Visita 4 e completato il washout post-trattamento di 1 settimana nello Studio SPD489-325.
3. Per i centri in cui lo Studio SPD489-326 (disegno con 12-mesi in aperto) era disponibile al momento della visita finale del soggetto nello Studio SPD489-325, il soggetto deve aver soddisfatto tutti i criteri di ingresso ed essere stato reclutato nello studio antecedente (SPD489 326).
4. Per i centri in cui lo Studio SPD489-326 (disegno randomizzato con possibile ritiro) era disponibile al momento della visita finale del soggetto nello Studio SPD489-325, il soggetto deve aver soddisfatto tutti i criteri di ingresso per lo studio antecedente (SPD489-326) e deve, o aver completato la telefonata/visita di follow-up post-trattamento, o essere stato ritirato dallo studio durante il periodo di ritiro randomizzato poiche' rispondeva ai criteri di recidiva dello studio antecedente (SPD489 326).
5. Soggetto che ha partecipato a SPD489-317, ha completato 9 settimane di trattamento e ha terminato la visita di follow-up della sicurezza 1-settimana post-trattamento.
6. Soggetto che ha partecipato a uno studio SPD489 precedente (SPD489-317, SPD489-325, o SPD489-326) a ha avuto un intervallo di sospensione della partecipazione (ad es., >7 giorni) tra l’uscita dallo studio precedente e l’entrata nello studio in oggetto. Il punteggio totale ADHD-RS-IV del soggetto al Basale dello Studio SPD489-404 (Visita 0) deve essere ≥28.
Per i soggetti che non hanno partecipato a un altro studio SPD489:
7. Soggetto di sesso maschile o femminile di eta' compresa tra 6-17 anni compiuti al momento del rilascio del consenso allo studio.
8. Soggetto che soddisfa 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.
9. Soggetto con un punteggio ADHD-RS-IV totale al Basale (Visita 0) ≥28.
Per tutti i soggetti:
10. I soggetti di sesso femminile in grado di procreare (FOCP), devono avere un test di gravidanza sierico beta-HCG (gonadotropina corionica umana) negativo allo Screening (Visita –1) e un test di gravidanza urinario negativo al Basale (Visita 0), non devono allattare al seno e devono accettare di attenersi ai requisiti applicabili del protocollo in termini di contraccezione.
11. Un genitore, o un rappresentante legalmente riconosciuto (LAR) del soggetto, deve sottoscrivere il consenso informato e deve esistere una documentazione dell’assenso (se applicabile) da parte del soggetto, che indichi che quest’ultimo e' consapevole della natura sperimentale dello studio e delle procedure e restrizioni previste, in conformita' a International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6 e a tutte le normative di riferimento, prima di completare qualsiasi procedura correlata allo studio.
12. Il soggetto e il genitore/LAR devono essere disponibili a e in grado di attenersi a tutti i test e requisiti definiti in questo protocollo, inclusa la supervisione del dosaggio mattutino. Nello specifico, il genitore/LAR deve essere disponibile al risveglio, all’incirca alle 7 del mattino per dispensare la dose di Prodotto Sperimentale per tutta la durata dello studio.
13. Il soggetto deve avere misurazioni pressorie entro il 95° percentile per eta', sesso e altezza allo Screening (Visita 1) e |
|
| E.4 | Principal exclusion criteria |
For subjects who participated in another SPD489 study (SPD489-317, SPD489-325 and/or SPD489-326):
1. Subject has a current, controlled (requiring a restricted medication) 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, severe depressive or severe anxiety disorder) or other symptomatic manifestations, such as agitated states, marked anxiety, or tension that, in the opinion of the examining clinician, will contraindicate treatment with SPD489 or confound efficacy or safety assessments. Comorbid psychiatric diagnoses will be established using the Kiddie–Schedule for Affective Disorders and Schizophrenia for School-age Children–Present and Lifetime–Diagnostic Interview (K SADS-PL) and additional modules if warranted by the results of the initial interview. The K SADS Lifetime module will not be required if <2 months have elapsed since the subject’s last study visit. Participation in behavioural therapy is permitted.
2. Subject was terminated from a previous SPD489 study (SPD489-317, SPD489-325, or SPD489-326) for protocol non-adherence and/or subject non-compliance and/or experienced a serious adverse event (SAE) or AE resulting in termination from the previous study.
3. Subject experienced any clinically significant AEs in a prior SPD489 study (SPD489-317, SPD489 325, or SPD489 326) that, in the opinion of the Investigator, would preclude further exposure to SPD489.
4. Subject participated in a prior SPD489 study (SPD489-317, SPD489-325, or SPD489-326), had a gap in participation (eg, >7 days between exiting the previous study and entering this study), and has a positive urine drug result at Screening (Visit –1), with the exception of the subject’s current ADHD therapy.
5. Subject participated in a prior SPD489 study (SPD489-317, SPD489-325, or SPD489-326), had a gap in participation (eg, >7 days between exiting the previous study and entering this study), and has taken another Investigational Product or taken part in another clinical study within 30 days prior to Screening (Visit –1).
For subjects who have not participated in another SPD489 study:
6. Subject has a positive urine drug result at Screening (Visit –1), with the exception of the subject’s current ADHD therapy.
7. Subject has a current, controlled (requiring a restricted medication) 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, severe depressive or severe anxiety disorder) or other symptomatic manifestations, such as agitated states, marked anxiety, or tension that, in the opinion of the examining clinician, will contraindicate treatment with SPD489 or confound efficacy or safety assessments. Comorbid psychiatric diagnoses will be established using the K-SADS-PL and additional modules if warranted by the results of the initial interview. Participation in behavioural therapy is permitted.
8. Subject has taken another Investigational Product or taken part in a clinical study within 30 days prior to Screening (Visit 1).
For all subjects:
9. Subject weighs <22.7kg (50lbs) or is significantly underweight based on World Health Organization Body Mass Index (BMI)-for-age sex specific charts at Screening (Visit –1). Significantly underweight is defined as a BMI <3rd percentile for this study.
10. Subject has a conduct disorder. Oppositional defiant disorder is not exclusionary.
11. Subject has a concurrent chronic or acute illness (such as severe allergic rhinitis or an infectious process |
Per i soggetti che hanno partecipato a un altro studio SPD489 (SPD489-317, SPD489-325 e/o SPD489-326):
1. Il soggetto presenta una diagnosi psichiatrica comorbile in atto, controllata (che necessita di un farmaco ad uso ristretto) o incontrollata, con sintomi significativi, come un qualsiasi disordine grave di Asse II o disordine grave di Asse I (quali disturbo post traumatico da stress, psicosi, malattia bipolare, disturbo ossessivo compulsivo grave a invasivita' progressiva, disturbo depressivo grave o disturbo d’ansia grave), o altre manifestazioni sintomatiche, come stati agitativi, ansia marcata, o tensione che, in base all’opinione del medico esaminante, risultano controindicati per il trattamento con SPD489, o potrebbero confondere le valutazioni di efficacia, o sicurezza. Le diagnosi psichiatriche comorbili saranno accertate utilizzando l’Intervista diagnostica per la valutazione dei disturbi psicopatologici in bambini e adolescenti - K SADS-PL (Kiddie–Schedule for Affective Disorders and Schizophrenia for School-age Children–Present and Lifetime–Diagnostic Interview) e ulteriori moduli, se necessari in base ai risultati dell’intervista iniziale. Il modulo K SADS Lifetime non sara' necessario se sono trascorsi <2 mesi dall’ultima visita di studio del soggetto. E’ consentita la partecipazione a una terapia comportamentale.
2. Il soggetto e' stato ritirato da uno studio SPD489 precedente (SPD489-317, SPD489-325, o SPD489-326) per la mancata adesione al protocollo e/o per la non-compliance e/o per lo sviluppo di un evento avverso grave (SAE), o AE che ha determinato la terminazione dello studio precedente.
3. Il soggetto ha sviluppato un qualsiasi AE clinicamente significativo in uno studio SPD489 precedente (SPD489-317, SPD489 325, o SPD489 326) che, secondo l’opinione dello Sperimentatore, potrebbe precludere un’ulteriore esposizione a SPD489.
4. Il soggetto ha partecipato a uno studio SPD489 precedente (SPD489-317, SPD489-325, o SPD489-326), ha avuto un intervallo di sospensione della partecipazione (ad es., >7 giorni tra l’uscita dallo studio precedente e l’entrata nello studio in oggetto) e presenta un risultato urinario farmacologico positivo allo Screening (Visita –1), fatta eccezione per la terapia in corso per ADHD.
5. Il soggetto ha partecipato a uno studio SPD489 precedente (SPD489-317, SPD489-325, o SPD489-326), ha avuto un intervallo di sospensione della partecipazione (ad es., >7 giorni tra l’uscita dallo studio precedente e l’entrata nello studio in oggetto) e ha assunto un altro Prodotto Sperimentale o ha partecipato a un altro studio clinico entro 30 giorni prima dello Screening (Visita –1).
Per i soggetti che non hanno partecipato a un altro studio SPD489:
6. Il soggetto presenta un risultato urinario farmacologico positivo allo Screening (Visita –1), fatta eccezione per la terapia in corso per ADHD.
7. Il soggetto presenta una diagnosi psichiatrica comorbile in atto, controllata (che necessita di un farmaco ad uso ristretto ) o incontrollata, con sintomi significativi, come un qualsiasi disordine grave di Asse II o disordine grave di Asse I (quali disturbo post traumatico da stress, psicosi, malattia bipolare, disturbo ossessivo compulsivo grave, a invasivita' progressiva, disturbo depressivo grave o disturbo d’ansia grave), o altre manifestazioni sintomatiche, come stati agitativi, ansia marcata, o tensione che, in base all’opinione del medico esaminante, risultano controindicati per il trattamento con SPD489, o potrebbero confondere le valutazioni di efficacia, o sicurezza. Le diagnosi psichiatriche comorbili saranno accertate utilizzando K SADS-PL e ulteriori moduli, se necessari in base ai risultati dell’intervista iniziale. E’ consentita la partecipazione a una terapia comportamentale.
8. Il soggetto ha assunto un altro Prodotto Sperimentale o ha partecipato a un altro studio clinico ent |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| long-term safety of SPD489 |
| sicurezza a lungo termine di SPD489 |
|
| 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 | No |
| 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 | 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| 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 | 68 |
| 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 | 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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