| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| 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 |
|
| 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 assess the efficacy of once daily dosing with optimised SPD503 compared to placebo in the treatment of children and adolescents aged 6 17 years with a diagnosis of Attention Deficit/Hyperactivity Disorder (ADHD) as measured by the ADHD Rating Scale-IV (ADHD-RS-IV). |
| L’obiettivo primario del presente studio e' valutare l’efficacia della monosomministrazione giornaliera di SPD503 ottimizzato rispetto al placebo nel trattamento di bambini e adolescenti di eta' compresa tra 6 e 17 anni con una diagnosi di sindrome da deficit di attenzione e iperattivita' (Attention Deficit/Hyperactivity Disorder, ADHD) in base alla valutazione ADHD-RS-IV (ADHD Rating Scale-IV). |
|
| E.2.2 | Secondary objectives of the trial |
Secondary:
1. To evaluate efficacy based on the clinician’s global impressions of ADHD severity and improvement as measured by the Clinical Global Impression-Severity (CGI-S) Scale and the Clinical Global Impression Improvement (CGI-I) Scale.
2. To evaluate efficacy on ADHD functional outcomes as measured by the Weiss Functional Impairment Rating Scale-Parent (WFIRS-P).
3. 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).
4. To evaluate the safety of SPD503 and STRATTERA based on the occurrence of treatment-emergent adverse events (TEAEs), electrocardiogram (ECG) results, vital signs, clinical laboratory results, and results from the Brief Psychiatric Rating Scale for Children (BPRS-C), a structured side-effect questionnaire, and Columbia-Suicide Severity Rating Scale.
5. To evaluate the efficacy of STRATTERA compared to placebo based on ADHD-RS, CGI-I, CGI-S, and HUI-2/3. |
Secondari:
1.Valutare l’efficacia in base alle impressioni generali del medico sulla severita' e sui miglioramenti dell’ADHD facendo riferimento alle scale CGI-S e CGI-I ;
2.Valutare l’efficacia in base ai risultati funzionali dell’ADHD secondo la scala WFIRS-P;
3.Valutare l’impatto del trattamento in base alla percezione delle preferenze dello stato di salute utilizzando gli HUI-2/3;
4.Valutare la sicurezza di SPD503 e STRATTERA in base alla comparsa di eventi avversi durante il trattamento (Treatment-Emergent Adverse Events, TEAEs), ai risultati dell’elettrocardiogramma (ECG), ai segni vitali, ai risultati degli esami clinici di laboratorio, ai risultati del BPRS-C (Brief Psychiatric Rating Scale for Children), al questionario strutturato sugli effetti indesiderati e alla scala di valutazione C-SSRS (Columbia-Suicide Severity Rating Scale).
5. Valutare l’efficacia di STRATTERA rispetto al placebo in base ad ADHD-RS, CGI-I, CGI-S e HUI-2/3. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Inclusion Criteria
The subject cannot be randomised before all inclusion criteria (including test results) are confirmed. Subjects meeting all of the criteria below may be included in the study. To be eligible for inclusion, each subject must meet each of the following criteria at Screening (Visit 1) and must continue to fulfil these criteria at Baseline (Visit 2) (if reassessed), unless otherwise noted:
1. Male or female, aged 6 17 years at the time of consent/assent at Screening (Visit 1).
2. 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 Good Clinical Practice Guidance E6, and applicable regulations before completing any study-related procedures at Screening (Visit 1).
3. Subject meets Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, 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).
4. Subject has a minimum ADHD-RS-IV total score of 32 at Baseline (Visit 2).
5. Subject has a minimum CGI-S score of 4 at Baseline (Visit 2).
6. Subject is functioning at an age-appropriate level intellectually, as judged by the Investigator.
7. Subject and parent/LAR understand, are willing, able, and likely to fully comply with the study procedures and restrictions defined in this protocol.
8. Subject is able to swallow intact tablets and capsules.
9. Subject who is a female of child-bearing potential (FOCP), defined as 9 years of age or <9 years of age and is menarchal, 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 2) and agree to comply with any applicable contraceptive requirements of the protocol.
10. Subject has a supine and standing BP measurement within the 95th percentile for age, sex and height. |
Il soggetto non puo' essere randomizzato se prima non vengono confermati tutti i criteri di inclusione (compresi i risultati delle analisi). I soggetti che soddisfano tutti i criteri descritti di seguito possono essere inclusi nello studio. Per poter essere incluso, il soggetto deve soddisfare ciascuno dei criteri descritti di seguito durante lo screening (Visita 1) e deve continuare a soddisfare tali criteri al basale (Visita 2) (se riesaminato), salvo diversamente stabilito:
1. Deve essere di sesso maschile o femminile, di eta' compresa tra 6 e 17 anni al momento del consenso/assenso allo screening (Visita 1).
2. Prima di passare alle procedure di screening (Visita 1) correlate allo studio, il genitore o rappresentante legalmente autorizzato (Legally Authorised Representative, LAR) del soggetto deve apporre la propria firma sul modulo relativo al consenso informato, inoltre deve essere fornito un documento di assenso (laddove possibile) del soggetto in questione attestante la consapevolezza da parte del soggetto circa la natura sperimentale dello studio e le procedure e restrizioni necessarie in conformita' con quanto stabilito dalla Conferenza Internazionale sulle linee guida per l’armonizzazione della buona prassi clinica E6 e con i regolamenti vigenti.
3. Il soggetto deve soddisfare i criteri del DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision) relativi alla diagnosi primaria di ADHD, sottotipo combinato, sottotipo iperattivo/impulsivo o disattento sulla base di una valutazione psichiatrica approfondita utilizzando il K-SADS-PL (Kiddie Schedule for Affective Disorders and Schizophrenia – Present and Lifetime version).
4. Al basale (Visita 2) il soggetto deve ottenere un punteggio minimo totale ADHD-RS-IV di 32.
5. Al basale (Visita 2) il soggetto deve ottenere un punteggio minimo CGI-S di 4.
6. Il soggetto deve avere un’attivita' intellettuale appropriata alla sua eta', in base al giudizio dello sperimentatore.
7. Il soggetto e il genitore/LAR comprendono, desiderano e sono in grado di rispettare totalmente le procedure e le restrizioni dello studio definite nel presente protocollo.
8. Il soggetto e' in grado di ingerire compresse e capsule intere.
9. I soggetti di sesso femminile in eta' fertile (Female Of Child-Bearing Potential, FOCP), di 9 anni di eta' o di eta' inferiore, alle quali sia comparso il menarca, devono risultare negative al test di gravidanza sierico beta hCG (Human Chorionic Gonadotropin) durante lo screening (Visita 1) e al test di gravidanza delle urine al basale (Visita 2) e devono acconsentire ad adottare le eventuali misure contraccettive previste dal protocollo.
10. In posizione supina ed eretta il soggetto ha una PA compresa nel 95° percentile in base all’eta', al sesso e all’altezza. |
|
| E.4 | Principal exclusion criteria |
Subjects are excluded from the study if any of the following criteria are met at Screening (Visit 1) or at Baseline (Visit 2) (if reassessed), unless otherwise noted:
1. Subject has any 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 (PTSD), bipolar illness, psychosis, pervasive developmental disorder, obsessive-compulsive disorder (OCD), 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 treatment with SPD503 or STRATTERA or confound efficacy or safety assessments.
2. Subject has any condition or illness including clinically significant abnormal Screening (Visit 1) laboratory values which, in the opinion of the Investigator, represents an inappropriate risk to the subject and/or could confound the interpretation of the study. Mild stable asthma treated without the use of beta-2 agonist is not exclusionary.
3. Subject has a known history or presence of structural cardiac abnormalities, cardiovascular or cerebrovascular disease, serious heart rhythm abnormalities, syncope, tachycardia, cardiac conduction problems (eg, clinically significant heart block or QT interval prolongation), exercise related cardiac events including syncope and pre syncope, or clinically significant bradycardia.
4. Subject has a known family history of sudden cardiac death, ventricular arrhythmia, or QT prolongation.
5. Subjects with orthostatic hypotension or a known history of hypertension.
6. Subject has glaucoma.
7. Subject has clinically significant ECG findings as judged by the Investigator with consideration of the central ECG laboratory’s interpretation.
8. Subject has a history of a seizure disorder (other than a single childhood febrile seizure occurring before the age of 3 years) or the presence of a serious tic disorder including Tourette’s Syndrome.
9. Current use of any prohibited medication or other medications, including monoamine oxidase inhibitors, herbal supplements, that affect BP or heart rate, potent CYP2D6 inhibitors, medicines known to prolong the QT/QTc interval, medications that lower seizure threshold, pressor agents, beta-2 agonists, medications that affect noradrenaline, medications that have 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 [ie, antihistamines]) in violation of the protocol specified washout criteria at Baseline (Visit 2).
10. 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.
11. Subject has taken another investigational product within 30 days prior to Baseline (Visit 2).
12. Subject is significantly overweight based on Center for Disease Control and Prevention Body Mass Index (BMI)-for-age gender specific charts at the Screening (Visit 1). Significantly overweight is defined as a BMI >95th percentile.
13. Children aged 6 12 years with a body weight of less than 25.0kg or adolescents aged 13 17 years with a body weight of less than 34.0kg or greater than 91.0kg at Screening (Visit 1). |
Sono esclusi dallo studio i soggetti che soddisfano uno o piu' dei criteri descritti di seguito durante lo screening (Visita 1) o al basale (Visita 2), salvo diversamente stabilito:
1. Soggetti con una diagnosi psichiatrica comorbida controllata (che richiede un farmaco proibito o un programma di modificazione del comportamento) o non controllata [tranne il disturbo opposizionale ( Oppositional Defiant Disorder, ODD)], compresi disturbi comorbidi severi dell’Asse II o I, quali disturbo post-traumatico da stress (Post Traumatic Stress Disorder, PTSD), sindrome bipolare, psicosi, disturbo pervasivo dello sviluppo, disturbo ossessivo-compulsivo (Obsessive-Compulsive Disorder, OCD), disturbo da abuso di sostanze o altre manifestazioni o anamnesi di malattia bipolare, psicosi o disturbi della condotta, che secondo lo sperimentatore, controindicano il trattamento con SPD503 o STRATTERA o confondono le valutazioni sull’efficacia e sulla sicurezza.
2. Soggetti che presentano condizioni o malattie tra cui valori anomali degli esami di laboratorio clinicamente significativi durante lo screening (Visita 1), che, secondo lo sperimentatore, rappresentano un rischio improprio per il soggetto e/o possono confondere l’interpretazione dello studio. La presenza di asma stabile di lieve entita' trattata senza l’utilizzo di agonisti beta-2 non esclude la possibilita' per il soggetto di partecipare allo studio.
3. Soggetti con un’anamnesi o con presenza di anomalie cardiache strutturali, malattie cardiovascolari o cerebrovascolari, serie anomalie del ritmo cardiaco, sincope, tachicardia, problemi di conduzione cardiaca (ad es. blocco cardiaco clinicamente significativo o prolungamento dell’intervallo QT), eventi cardiaci correlati all’esercizio fisico, compresa la sincope e la presincope, o bradicardia clinicamente significativa.
4. Soggetti con una storia familiare di morte cardiaca improvvisa, aritmia ventricolare o prolungamento del QT.
5. Soggetti con ipotensione ortostatica o con un’anamnesi di ipertensione.
6. Soggetti con glaucoma.
7. Soggetti con risultati ECG clinicamente significativi, valutati dallo sperimentatore con la consulenza del laboratorio ECG centrale.
8. Soggetti con un’anamnesi di convulsioni (diverse dalle singole convulsioni febbrili infantili che si possono verificare durante i primi 3 anni di eta') o con seri tic, compresa la sindrome di Tourette.
9. Utilizzo corrente di farmaci proibiti o altri medicinali, compresi gli inibitori della monoaminoossidasi, gli integratori a base di erbe, che incidono sulla PA o sulla frequenza cardiaca, i potenti inibitori CYP2D6, i farmaci noti come prolungatori dell’intervallo QT/QTc, i medicinali che abbassano la soglia convulsiva, gli agenti che agiscono sulla pressione arteriosa, gli agonisti beta-2, i medicinali che incidono sulla noradrenalina, sull’SNC o sulle prestazioni cognitive, come ad esempio gli antistaminici sedativi e i simpatomimetici decongestionanti (sono consentiti i broncodilatatori inalanti) o un’anamnesi di utilizzo cronico di sedativi [cioe' antistaminici] al basale (Visita 2) che violano i criteri relativi al washout specificati nel protocollo.
10. Soggetti con un’anamnesi di abuso o dipendenza da alcool o altre sostanze negli ultimi 6 mesi, in base a quanto definito nel DSM-IV-TR (ad eccezione della nicotina).
11. Soggetti che hanno assunto altri prodotti sperimentali 30 giorni prima del basale (Visita 2).
12. Soggetti che durante lo screening (Visita 1) risultano notevolmente sovrappeso rispetto alle tabelle con rapporto eta'/sesso/indice di massa corporea (Body Mass Index, BMI) del Centro per il controllo delle malattie e la prevenzione. Con il termine “notevole sovrappeso” ci si riferisce a un BMI superiore al 95° percentile.
13. Bambini di eta' compresa tra 6 e 12 anni con un peso inferiore a 25 kg o adolescenti di eta' compresa tra 13 e 17 anni con un pe |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change from baseline score of the ADHD-RS-IV total score at end-poit. |
| Cambiamento del score ADHD-RS-IV tra baselineal end-point |
|
| 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 | Yes |
| 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) | 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 | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 36 |
| 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
| |
| 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 | 20 |
| 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 |
Print
