Safety and Tolerability Study of SPD489 in Preschool Children Aged 4-5 Years, Diagnosed With Attention-deficit/Hyperactivity Disorder
Condition: Attention Deficit Hyperactivity Disorder (ADHD)
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity
Intervention: SPD489
Intervention description: Participants will receive 5 mg of SPD489 capsule orally once daily in the morning and titrated in a step-wise fashion up to either 10 mg, 15 mg, 20 mg, or 30 mg until an optimal dose was reached.
Intervention MeSH terms: Lisdexamfetamine Dimesylate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 113.0
Sex: All
Minimum age: 4 Years
Maximum age: 5 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the long-term safety of SPD489 administered as a
      daily morning dose (5, 10, 15, 20, and 30 mg/day) in preschool children diagnosed with
      Attention-deficit/Hyperactivity Disorder (ADHD).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Participant is male or female aged 4-5 years inclusive at the time of consent from
             antecedent studies SPD489-211 or SPD489-347 or at the time of consent if directly
             enrolled.

          2. Before completing any study-related procedures, participant's parent(s) or legally
             authorized representative (LAR) must provide signature of informed consent, and there
             must be documentation of assent (if applicable) by the participant indicating that the
             participant is aware of the investigational nature of the study. The participant's
             parent(s) or LAR should understand that the required procedures and restrictions are
             being conducted in accordance with the International Council of Harmonisation (ICH)
             Good Clinical Practice (GCP) Guideline E6 (1996), any updates or revisions, and
             applicable federal or local regulations.

          3. Participant and parent(s)/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 parent/LAR should be available at approximately 7:00AM (+2 hours) to
             dispense the dose of investigational product for the duration of the study.

          4. Roll-over participant from antecedent SPD489-347 study:

             a. Participant completed the antecedent study (SPD489-347)

          5. Direct enrolled participants must meet antecedent study inclusion criteria, as listed
             below

               1. Participant must meet Diagnostic and Statistical Manual of Mental Disorders,
                  Fourth Edition (DSM-IV-TR) criteria for a primary diagnosis of ADHD (any subtype)
                  based on a detailed psychiatric evaluation conducted by a sponsor-approved
                  clinician

               2. Participant has an attention-deficit/hyperactivity disorder rating scale- IV
                  (ADHD-RS-IV) Preschool Version total score at the Baseline Visit (Visit 0) of
                  greater than equals to (>=) 28 for boys and >= 24 for girls.

               3. Participant has a Clinical Global Impressions - Severity of Illness (CGI-S) score
                  >=4 at the Baseline Visit (Visit 0).

               4. Participant has a Peabody Picture Vocabulary Test, Fourth Edition standard score
                  of >=70 at the Screening Visit (Visit -1).

               5. Participant has undergone an adequate course of non-pharmacological treatment
                  based on investigator judgment or the participant has a severe enough condition
                  to consider enrollment without undergoing prior non-pharmacological treatment,
                  based on investigator judgment.

               6. Participant has, in the opinion of the investigator, participated in a structured
                  group activity (eg, preschool, sports, Sunday school) so as to assess symptoms
                  and impairment in a setting outside the home.

               7. Participant has lived with the same parent(s) or guardian for >=6 months.

        Exclusion Criteria:

          1. Participant was terminated from an antecedent SPD489 study for non-compliance and/or
             experienced a serious adverse event (SAE) or adverse event (AE) resulting in
             termination.

          2. Participant is required to or anticipates the need to take medications that have
             central nervous system effects or affect performance, such as, but not limited to,
             sedating antihistamines and decongestant sympathomimetics, or monoamine oxidase
             inhibitors. Stable use of bronchodilator inhalers is not exclusionary.

          3. Participant has a concurrent chronic or acute illness (such as, but not limited to,
             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 participant. Similarly, the participant
             will be excluded if he or she has any additional condition(s) that, in the
             investigator's opinion, would prohibit the participant from completing the study or
             would not be in the best interest of the participant. The additional condition(s)
             would include any significant illness or unstable medical condition that could lead to
             difficulty complying with the protocol. Mild, stable asthma is not exclusionary.

          4. Participant has a documented allergy, hypersensitivity, or intolerance to amphetamine
             or to any excipients in the investigational product.

          5. Participant has a known family history of sudden cardiac death or ventricular
             arrhythmia.

          6. Participant has a blood pressure measurement >= 95th percentile for age, sex, and
             height at the screening visit (Visit -1) or the baseline visit (Visit 0) or a history
             of moderate or severe hypertension.

          7. Participant has a known history of symptomatic cardiovascular disease, unexplained
             syncope, exertional chest pain, 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.

          8. Participant is taking any medication that is excluded per the protocol.

          9. Participant had any clinically significant electrocardiogram (ECG) or clinical
             laboratory abnormalities at the Screening Visit (Visit -1) or baseline visit (Visit
             0), based on investigator judgment.

         10. Participant has a history of hyperthyroidism, or current abnormal thyroid function,
             defined as abnormal thyroid stimulating hormone (TSH) and thyroxine (T4) at the
             Screening Visit (Visit-1) or Visit 0. Treatment with a stable dose of thyroid
             medication for at least 3 months is permitted.

         11. Participant has taken another investigational product or has taken part in a clinical
             study within 30 days prior to the Screening Visit (Visit -1).

         12. Participant is well-controlled on his/her current ADHD medication with acceptable
             tolerability.

         13. Participant has glaucoma.

         14. Participant has failed to fully respond, based on investigator judgment, to an
             adequate course of amphetamine therapy.

         15. Participant has a current, controlled (requiring medication or therapy) or
             uncontrolled, comorbid psychiatric disorder including but not limited to any of the
             below co-morbid Axis I disorders and Axis II disorders:

               1. post-traumatic stress disorder (PTSD) or adjustment disorder

               2. bipolar illness, psychosis, or family history of these disorders

               3. pervasive developmental disorder

               4. obsessive-compulsive disorder (OCD)

               5. psychosis/schizophrenia

               6. participant has a serious tic disorder, or a family history of Tourette's
                  disorder

               7. participant 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. Participants with
                  intermittent passive suicidal ideation are not necessarily excluded based on the
                  assessment of the investigator

               8. a history of physical, sexual, or emotional abuse

               9. any other disorder or agitated state that in the opinion of the investigator,
                  contraindicates SPD489 or lisdexamfetamine dimesylate treatment or confound
                  efficacy or safety assessments.

         16. Participant has initiated behavioral therapy within 1 month of the baseline visit
             (Visit 0). Participant may not initiate behavioral therapy during the study.

         17. Participant has a height <=5th percentile for age and sex at the screening visit
             (Visit -1).

         18. Participant has a weight <=5th percentile for age and sex at the screening visit
             (Visit -1).

         19. Participant lives with anyone who currently abuses stimulants or cocaine.

         20. Participant has a history of seizures (other than infantile febrile seizures).