Safety and Efficacy of SPD489 on Executive Function Behaviors in Adults With Attention-Deficit/Hyperactivity Disorder (ADHD)
Condition: ADHD Specifically With Executive Function Impairment
MeSH terms: Attention Deficit Disorder with Hyperactivity
Intervention: SPD489; Placebo
Intervention description: 1 capsule per day (30, 50 or 70 mg), daily throughout the double-blind treatment period (10 weeks); 1 capsule per day, daily throughout the double-blind treatment period (10 weeks)
Intervention MeSH terms: Lisdexamfetamine Dimesylate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 161.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No

Summary:

      The primary objective of the study is to evaluate the efficacy of SPD489 compared to placebo
      on executive function (self-regulation) behaviors in adults with ADHD who report clinically
      significant impairment of executive function behavior in their everyday environment, as
      measured by the self-report Behavior Rating Inventory of Executive Function - Adult Version
      (BRIEF-A) Global Executive Composite (GEC) T-score.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subject must be 18-55 years of age, inclusive at the time of consent.

          2. Subject has an established close relationship of at least 6-months duration before
             screening (Visit -1) with an informant who will be able to observe and be willing to
             report on the subject's behavior and symptoms in multiple social settings during the
             course of the study. Informant is defined as a person who has a domicile relationship
             with the subject. When applicable, the informant should be the subject's
             spouse/significant other. Additionally, the informant cannot participate as a subject
             in the study and can only serve as the informant for a single subject.

          3. Subject has a lifestyle that in the opinion of the Investigator will enable the
             subject to complete all study testing and requirements defined in the protocol.

          4. Female subjects 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) and agree to comply with any applicable contraceptive requirements of the
             protocol.

          5. Subject meets the Diagnostic and Statistical Manual of Mental Disorders, Fourth
             Edition - Text Revision (DSM-IV-TR) criteria for a primary diagnosis of ADHD
             (diagnostic code 314.00 and 314.01) established by a comprehensive psychiatric
             evaluation that reviews DSM-IV-TR criteria with at least 6 of the 9 subtype criteria
             met. The Adult ADHD Clinical Diagnostic Scale version 1.2 (ACDS v1.2) will be utilized
             as the diagnostic tool.

          6. Subject has a total score of ≥65 on BRIEF-A GEC T-score by self-report at baseline
             (Visit 0).

          7. Subject has a total score of ≥28 using the Adult ADHD-RS with prompts at baseline
             (Visit 0).

          8. Subject must have a minimum level of intellectual functioning as determined by the
             Investigator at screening (Visit -1).

          9. Subject is able to swallow a capsule.

         10. Subject is willing and able to comply with all the testing and requirements defined in
             this protocol.

         11. Subject and informant must be able to provide written, personally signed and dated
             informed consent to participate in the study in accordance with the International
             Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines and
             applicable regulations before completing any study related procedures.

        Exclusion Criteria

          1. Subject has a current comorbid psychiatric disorder that is either controlled with
             medications prohibited in this study or is uncontrolled and associated with
             significant symptoms. Prohibited disorders include those associated with diagnoses
             including but not limited to any severe comorbid Axis II disorder or severe Axis I
             disorder (such as Post Traumatic Stress Disorder [PTSD], psychosis, bipolar illness,
             pervasive developmental disorder, severe obsessive compulsive disorder, severe
             depressive or severe anxiety disorder). Other symptomatic manifestations (such as
             agitated states) that contraindicate treatment with SPD489 or confound efficacy or
             safety assessments in the opinion of the examining physician are also prohibited.
             Comorbid psychiatric diagnoses will be established by the psychiatric evaluation that
             includes the Structured Clinical Interview for DSM-IV-TR disorders (SCID-I).

          2. Subjects who are currently considered a suicide risk, any subject who has previously
             made a suicide attempt or those who are currently demonstrating active suicidal
             ideation.

          3. The subject has a body mass index (BMI) of <18.5 or ≥40.

          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 administered 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. This 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 a history of seizures (other than infantile febrile seizures), any tic
             disorder, a current diagnosis and/or a known family history of Tourette's Disorder.

          6. Subject has known history of symptomatic cardiovascular disease, advanced
             arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm
             abnormalities, coronary artery disease, transient ischemic attack or stroke or other
             serious cardiac problems that may place them at increased vulnerability to the
             sympathomimetic effects of a stimulant drug.

          7. Subject has a known family history of sudden cardiac death or ventricular arrhythmia.

          8. Subject has any clinically significant ECG or clinically significant laboratory
             abnormality at screening (Visit -1).

          9. Subject has current abnormal thyroid function, defined as abnormal screening thyroid
             stimulating hormone (TSH) and thyroxine (T4). Treatment with a stable dose of thyroid
             medication for at least 3 months is permitted.

         10. Subject has a history of moderate to severe hypertension or has a resting sitting
             systolic blood pressure >139mmHg or diastolic blood pressure >89mmHg. Subjects with
             well-controlled mild or moderate hypertension on a single antihypertensive agent are
             allowed. Combination antihypertensive medications are not allowed.

         11. Subject is taking any medication that is excluded.

         12. Subject has a documented allergy, hypersensitivity, or intolerance to amphetamines.

         13. Subject has a documented allergy, hypersensitivity, or intolerance to any excipients
             in the investigational medicinal product.

         14. Subject has failed to respond to one or more adequate courses (dose and duration) of
             amphetamine therapy.

         15. 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 criteria.

         16. Subject has a positive urine drug result at screening (Visit -1) (with the exception
             of subject's current stimulant therapy, if any).

         17. Subject has taken an investigational drug or taken part in a clinical trial, including
             an SPD489 clinical trial, within 30 days prior to screening (Visit -1).

         18. Subject has glaucoma.

         19. Subject is taking other medications that have central nervous system (CNS) effects or
             affect performance, such as sedating antihistamines and decongestant sympathomimetics,
             or are monoamine oxidase inhibitors (during or within 7 days of investigational
             medicinal product administration). Stable use of bronchodilator inhalers is not
             exclusionary.

         20. Subject is female and pregnant or lactating.

         21. Subjects who have previously been randomized into this study and subsequently
             withdrawn.

         22. Subject is well controlled on their current ADHD medication with acceptable
             tolerability.