Safety, Tolerability, Pharmacokinetic, and Efficacy Study of SPD489 in Preschool Children With Attention-deficit/Hyperactivity Disorder

A Phase 2, Open-label, Multicenter, Exploratory Safety, Tolerability, Pharmacokinetic, and Efficacy Study of SPD489 in Preschool Children Aged 4-5 Years With Attention-deficit/Hyperactivity Disorder

The purpose of this study is to gain initial safety, tolerability, pharmacokinetic, and efficacy information on SPD489 in preschool children 4-5 years old who are diagnosed with ADHD. Generating such data will provide data on the use of SPD489 in the preschool ADHD population.

Inclusion Criteria:

1. Subject is a male or female aged 4-5 years inclusive at the time of consent. Only recruiting male subjects as of December 2015
2. Subject's parent or LAR must provide signature of informed consent, and there must be documentation of assent (if applicable) by the subject in accordance with the ICH GCP Guideline E6 (1996) and applicable regulations, before completing any study-related procedures.
3. Subject and parent/LAR are willing and able to comply with all of the testing and requirements defined in the protocol, including oversight of morning dosing. Specifically, the same parent/LAR should be available daily to dispense the dose of investigational product for the study duration.
4. Subject must meet DSM-IV-TR criteria for a primary diagnosis of ADHD (all subtypes) based on a detailed psychiatric evaluation conducted by a sponsor-approved clinician
5. Subject has an ADHD-RS-IV Preschool Version total score ≥93rd percentile at the Baseline Visit (Visit 0). For boys, this is a score of ≥32. For girls, this is a score of ≥24.
6. Subject has a CGI-S score ≥4 at the Baseline Visit (Visit 0).
7. Subject has a Peabody Picture Vocabulary Test, Fourth Edition standard score of ≥70 at the Screening Visit (Visit -1).
8. Subject has undergone an adequate course of non-pharmacological treatment based on investigator judgment or the subject has a severe enough condition to consider enrollment without undergoing prior non-pharmacological treatment based on investigator judgment.
9. Subject has, in the opinion of the investigator, participated in a structured group activity (e.g., preschool, sports, Sunday school) so as to assess symptoms and impairment in a setting outside the home.
10. Subject has lived with the same parent/LAR for ≥6 months.

Exclusion Criteria:

1. Subject is required to or anticipates the need to take medications that have CNS effects or affect performance, such as sedating antihistamines and decongestant sympathomimetics, or are taking monoamine oxidase inhibitors. Stable use of bronchodilator inhalers is not exclusionary.
2. Subject has taken another investigational product or has taken part in a clinical study within 30 days prior to the Screening Visit (Visit -1).
3. Subject is well controlled on his/her current ADHD medication with acceptable tolerability.
4. 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. Similarly, the subject will be excluded if he or she has any additional condition(s) that, in the investigator's opinion, would prohibit the subject from completing the study or would not be in the best interest of the subject. The additional conditions would include any significant illness or unstable medical condition that could lead to difficulty complying with the protocol. Mild, stable asthma is not exclusionary.
5. Subject has failed to fully respond, based on investigator judgment, to a previously administered adequate course of amphetamine therapy.
6. Subject has a documented allergy, hypersensitivity, or intolerance to amphetamine or to any excipients in the investigational product.
7. Subject has a known family history of sudden cardiac death or ventricular arrhythmia.
8. Subject has a blood pressure measurement ≥95th percentile for age, sex, and height at the Screening Visit (Visit -1) or the Baseline Visit (Visit 0).
9. 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 placing them at increased vulnerability to the sympathomimetic effects of a stimulant drug.
10. Subject has any clinically significant electrocardiogram at the Screening Visit (Visit -1) or the Baseline Visit (Visit 0) or clinically significant laboratory abnormalities at the Screening Visit (Visit -1) based on investigator judgment.
11. Subject has current abnormal thyroid function, defined as abnormal thyroid stimulating hormone and thyroxine at the Screening Visit (Visit -1). Treatment with a stable dose of thyroid medication for at least 3 months is permitted.
12. Subject has a current diagnosis of adjustment disorder, autism, psychosis, or bipolar disorder.
13. Subject is currently considered at risk for suicide in the opinion of the investigator, has previously made a suicide attempt, or is currently demonstrating active suicidal ideation. Subjects with intermittent passive suicidal ideation are not necessarily excluded, based on the assessment of the investigator.
14. Subject has a height ≤5th percentile for age and sex at the Screening Visit (Visit -1).
15. Subject has a weight ≤5th percentile for age and sex at the Screening Visit (Visit -1).
16. Subject has a history of seizures (other than infantile febrile seizures) or a current diagnosis of Tourette's disorder.
17. Subject has a chronic or current tic disorder that is judged by the investigator to be exclusionary.
18. Subject is taking any medication that is excluded.