| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Attention Deficit/Hyperactivity Disorder (ADHD) |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Behavioral Disciplines and Activities [F04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.1 |
| 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 |
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.
|
|
| 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). |
|
| 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, 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 (SPD489-317, SPD489-325, or SPD489-326).
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 SPD489-325.
3. For sites where Study SPD489-326 study (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 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 (See Section 4.3).
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) GCP Guideline E6 (1996) 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) (See Appendix 2.2 and Appendix 2.3 for Boys and Appendix 2.5 and Appendix 2.6 for Girls).
14. Subject is functioning at an age-appropriate level intellectually, as deemed by the study Investigator.
15. Subject is able to swallow a capsule. |
|
| E.4 | Principal exclusion criteria |
For subjects who participated in another SPD489 study (SPD489-317, SPD489-325, 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 or other symptomatic manifestations, such as agitated states, marked anxiety or tension.
2. Subject was terminated from a previous SPD489 study for protocol non-adherence and/or subject non-compliance and/or experienced an SAE or AE resulting in termination from the previous study.
3. Subject experienced any clinically significant AEs in a prior SPD489 study
4. Subject participated in a prior SPD489 study, 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
5. Subject participated in a prior SPD489 study, 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 trial 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, 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 or other symptomatic manifestations, such as agitated states, marked anxiety, or tension.
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).
10. Subject has a conduct disorder.
11. Subject has a concurrent chronic or acute illness (such as severe allergic rhinitis or an infectious process requiring antibiotics), disability, or other condition that might
confound the results of safety assessments conducted in the study or that might increase risk to the subject.
12. 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.
13. Subject has glaucoma.
14. Subject is significantly overweight based on World Health Organization Body Mass Index (BMI)-for-age and sex-specific charts at Screening (Visit –1).
15. Subject has current abnormal thyroid function, defined as abnormal thyroid stimulating hormone (TSH) and thyroxine (T4) at Screening (Visit –1). Treatment with a stable dose of thyroid medication for at least 3 months is permitted.
16. Subject has any clinically significant ECG at Screening (Visit –1) or Baseline (Visit 0).
17. Subject has any clinically significant laboratory abnormalities at Screening (Visit –1) or Baseline (Visit 0) if repeated.
18. Subject has a documented allergy, hypersensitivity, or intolerance to any active
ingredient or excipients in SPD489.
19. Subject has a recent history of suspected substance abuse or dependence disorder (excluding nicotine) in accordance with DSM-IV-TR criteria.
20. Subject has a history of seizures, a chronic or current tic disorder, a current diagnosis of Tourette’s Disorder, or a known family
history of Tourette’s Disorder.
21. Subject has a known history of symptomatic cardiovascular or cerebrovascular 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.
22. Subject has a known family history of sudden cardiac death or ventricular arrhythmia.
23. Subject is taking any medication that is excluded.
24. Subject has a medical condition, other than ADHD, that requires treatment with
medications that have central nervous system effects and/or affect performance. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint of this study is the long-term safety of SPD489. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| TEAEs: from the start of treatment to 3 days after cessation. Others: at each applicable post-baseline visit. |
|
| E.5.2 | Secondary end point(s) |
1. ADHD-RS-IV total score as well as the Hyperactivity/Impulsivity and Inattention subscale scores
2. The CGI-I and CGI-S |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Each applicable post-baseline visit until last visit on treatment |
|
| 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) | 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 | No |
| 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 | No |
| 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 | 4 |
| 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 | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Belgium |
| France |
| Italy |
| Netherlands |
| Romania |
| Sweden |
| Germany |
| Hungary |
| Spain |
| Poland |
| United Kingdom |
| United States |
|
| 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 | 2 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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