E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Attention Deficit / Hyperactivity Disorder (ADHD) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064104 |
E.1.2 | Term | ADHD |
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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 safety of LDX administered as a daily morning dose (30, 50, and 70mg/day) in the treatment of children and adolescents (6 -17 years of age inclusive at the time of consent for the antecedent study, SPD489-325) diagnosed with moderately symptomatic ADHD. The evaluation of safety will be based on the occurrence of treatment-emergent adverse events (TEAEs), specific evaluation of blood pressure and pulse, electrocardiogram (ECG) results, clinical laboratory test results, and physical examination findings.
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E.2.2 | Secondary objectives of the trial |
The key secondary objective of this study is to assess the long-term efficacy of LDX using the clinician administered ADHD-rating scale-IV (ADHD-RS-IV). The other secondary objectives of this study are:
1. To assess the long-term efficacy of LDX using a global clinical measure of improvement, the Clinical Global Impressions – Global Improvement (CGI-I).
2. To assess the impact of LDX on the perception of health state preferences and quality of life (QoL) over a 1 year period 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 over a 1 year period 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 LDX.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The subject cannot be enrolled before all inclusion criteria (including test results) are confirmed. Subjects meeting all of the criteria listed below will be included in the study:
1. 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.
2. 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 test product for the duration of the study.
3. Subject is a male or female aged 6-17 years inclusive at the time of consent for the antecedent study (SPD489-325).
4. Subject satisfied all entry criteria for the antecedent study (SPD489-325), and completed a minimum of 4 weeks of double-blind treatment, reached Visit 4 and completed the 1-week post-treatment washout in the antecedent study (SPD489-325), without experiencing any clinically significant adverse events (AEs) that would preclude exposure to LDX.
5. Subject must have a satisfactory medical assessment with no clinically significant or relevant abnormalities as determined by medical history, physical examination findings, and clinical laboratory tests results.
6. Subject has blood pressure measures within the 95th percentile for age, gender, and height.
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E.4 | Principal exclusion criteria |
Subjects are excluded from the study if any of the following criteria are met at Visit 1 or if they are reassessed:
1. Subject was terminated from SPD489-325 for non-compliance and/or experienced a serious adverse event (SAE) or AE resulting in termination from the antecedent study.
2. 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 LDX or confound efficacy or safety assessments. Comorbid psychiatric diagnoses will be established at the Screening Visit (Visit -1) of the antecedent study (SPD489-325) with the Screening interview of the Kiddie-SADS-Present and Lifetime – Diagnostic Interview (K-SADS-PL) and additional modules if warranted by the results of the initial interview. Participation in behavioural therapy, provided the subject was receiving the therapy for at least 1 month at the time of the Baseline Visit (Visit 0) of the antecedent study (SPD489-325).
3. Subject has a conduct disorder. Oppositional defiant disorder is not exclusionary.
4. Subject has any concurrent chronic or acute illness or unstable medical condition that could confound the results of safety assessments, increase risk to the subject or lead to difficulty complying with the protocol.
5. Subject is currently considered a suicide risk, has previously made a suicide attempt or has a prior history of, or is currently, demonstrating active suicidal ideation.
6. Subject is female and is pregnant or lactating.
7. Subject has glaucoma.
8. Subject has any clinically significant ECG at Visit 8 of the antecedent study (SPD489 325) or clinically significant laboratory abnormalities at Visit 7 of the antecedent study (SPD489-325).
9. Subject has a documented allergy, hypersensitivity, or intolerance to amphetamine.
10. Subject has a recent history (within the past 6 months) of suspected substance abuse or dependence disorder (excluding nicotine) in accordance with DSM-IV-TR ï€ criteria.
11. Subject has a history of seizures (other than infantile febrile seizures), a tic disorder, a current diagnosis and/or a known family history of Tourette’s Disorder.
12. Subject has a known history of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug.
13. Subject has a known family history of sudden cardiac death or ventricular arrhythmia.
14. Subject is taking any medication that is excluded.
15. Subject is taking other medications that have central nervous system (CNS) effects, affect performance, such as sedating antihistamines and decongestant sympathomimetics, or are monoamine oxidase inhibitors (during or within 14 days of test product administration). Stable use of bronchodilator inhibitors is not exclusionary.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is the long-term safety of LDX. Treatment-emergent adverse events, vital signs, clinical laboratory test results, physical examination findings, and ECG measurements will be utilised to evaluate the long-term safety of LDX.
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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) | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Extension of the antecedent study, SPD489-325 |
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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 | No |
E.8.2.3 | Other | No |
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 | 42 |
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 | Information not present in EudraCT |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |