| 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 |
| Attention Deficit/Hyperactivity Disorder (ADHD) |
|
| 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 and tolerability of SPD503. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are:
-To assess the maintenance of efficacy of SPD503 that was achieved in
the antecedent studies.
-To provide access to SPD503 for subjects following their participation in SPD503-315 or SPD503-316 for up to 2 years. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
For subjects enrolling from antecedent Study SPD503-315:
Subjects will be eligible if they met the response criteria for entry into Phase 2, were randomized, and completed Phase 2 or withdrew early because the protocol-defined treatment failure criteria was met.
For subjects enrolling from antecedent Study SPD503-316:
Children age 6-12, regardless of treatment group, must complete 10 weeks of double-blind treatment, reach Visit 15/Final, and complete the 2-week dose taper.
Adolescents age 13 and older, regardless of treatment group, must complete 13 weeks of double-blind treatment, reach Visit 15/Final, and complete the 2-week dose taper.
For all subjects:
1. For subjects where Study SPD503-318 was not available at the time of subject’s
final visit in the antecedent study (SPD503-315 or SPD503-316), subject may still screen unless they are well-controlled on another ADHD medication with acceptable tolerability and the parent/caregiver is satisfied with the current ADHD medication.
2. Subject satisfied all entry criteria for the antecedent study (SPD503-315 or
SPD503-316).
3. Subject who is a female of child-bearing potential (FOCP), defined as >9 years of age or <9 years of age and is post-menarchal, must have a negative serum beta Human Chorionic Gonadotropin (β-hCG) pregnancy test at the Screening Visit (Visit 1) and a negative urine pregnancy test at the Baseline Visit (Visit 2) and agree to comply with any applicable contraceptive requirements of the protocol.
4. 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.
5. Subject and parent/LAR are willing, able, and likely to fully comply with all the
testing and requirements defined in this protocol, including oversight of dosing.
Specifically, the parent/LAR must be available upon awakening, to dispense the
dose of investigational product for the duration of the study.
6. Subject has a supine and standing blood pressure (BP) measurement within the 95th percentile for age, sex, and height.
7. Subject is functioning at an age-appropriate level intellectually, as deemed by the Investigator.
8. Subject is able to swallow intact tablets. |
|
| E.4 | Principal exclusion criteria |
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 confound efficacy or safety assessments. Review the Kiddie Schedule for Affective Disorders and Schizophrenia –
Present and Lifetime version (K-SADS-PL) from the antecedent study to confirm
diagnosis, if necessary.
2. Subject who early terminated from Study SPD503-315 or Study SPD503-316 for protocol non-adherence, subject non-compliance, an adverse event (AE), serious adverse event (SAE), or withdrawal by subject.
3. Subject experienced any clinically significant AE in a prior SPD503 study (SPD503-315 or SPD503-316) that, in the opinion of the Investigator, would preclude exposure to SPD503.
4. Clinically important abnormality on urine drug and/or alcohol screen at the Screening Visit (Visit 1).
5. Subject has taken any investigational medicinal product as follows: last dose of
investigational product in Study SPD503-315 within 7 days prior to the Baseline Visit (Visit 2); investigational product in Study SPD503-316 within 30 days prior to the Baseline Visit (Visit 2); any other investigational product within 30 days prior to the Baseline Visit (Visit 2) or any other ADHD medication within 30 days prior to Baseline Visit (Visit 2).
6. Subject is significantly overweight based on Center for Disease Control and
Prevention Body Mass Index (BMI)-for-age sex-specific charts at the Screening Visit (Visit 1). Significantly overweight is defined as a BMI >95th percentile.
7. Children aged 6 to 12 years with a body weight of less than 25.0kg or adolescents aged 13 years and older with a body weight of less than 34.0kg at the Screening Visit (Visit 1).
8. Subject has any condition or illness including clinically significant abnormal
laboratory values at the Screening Visit (Visit 1) which, in the opinion of the
Investigator, represents an inappropriate risk to the subject and/or could confound the interpretation of the study.
9. 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.
10. Subject has clinically significant ECG findings, as judged by the Investigator with consideration of the central ECG laboratory’s interpretation, at the Baseline Visit (Visit 2).
11. Subject has a known or suspected allergy, hypersensitivity, or clinically significant intolerance to guanfacine hydrochloride, or any components found in SPD503.
12. 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.
13. 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.
14. 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.
15. Subject with orthostatic hypotension or a known history of controlled or uncontrolled hypertension.
16. Current use of any prohibited medication or other medications, including herbal supplements, that affect BP or heart rate or 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 [i.e., antihistamines]) in violation of the protocol specified washout
criteria at the Baseline Visit (Visit 2).
17. Subject has a medical condition, other than ADHD, that requires treatment with medications that have central nervous system effects and/or affect performance.
18. Subject is female and is pregnant or currently lactating.
19. Subject failed screening or was previously enrolled in this study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoints of this study are the long-term safety of SPD503 as follows:
• Occurrence of TEAEs from start of treatment to 3 days after cessation
• Specific evaluation of BP and pulse at each applicable post baseline visit
• ECG results at each applicable post baseline visit
• C-SSRS at each applicable post baseline visit
• Effects on growth will be assessed at each applicable post baseline visit. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints of the study are listed below:
• The change from baseline in ADHD-RS-IV total score and the hyperactivity/impulsivity and inattention subscale scores at each of Visits 3-19. Baseline will be defined in 2 ways; firstly as the Baseline Visit from the antecedent study, and secondly as Visit 2 from this study.
• The CGI-S at each of Visits 2-19 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this 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 | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| This study has been designed to provide up to 2 years access to SPD503 for European children and adolescents who participated in Study SPD503-315 or SPD503-316 and provides the opportunity to assess the long-term safety and efficacy within this population. |
|
| 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 | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 82 |
| 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 |
| Austria |
| Belgium |
| France |
| Germany |
| Ireland |
| Italy |
| Netherlands |
| Poland |
| Romania |
| Spain |
| Sweden |
| Turkey |
| Ukraine |
| United Kingdom |
|
| 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 | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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