A Flexible-Dose Titration Study of Aptensio XR in Children Ages 4 to Under 6 Years Diagnosed With ADHD
Condition: Attention Deficit Disorder With Hyperactivity
MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity
Intervention: Aptensio XR; Placebo
Intervention description: Optimized dose of Aptensio XR (10, 15, 20, 30 or 40 mg) administered orally, once daily; Placebo capsules
Intervention MeSH terms: Methylphenidate
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized, Double-Blind, Placebo-Controlled, Flexible-Dose Titration Study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Blinded active capsules looked identical to the same strength placebo capsules
Enrollment: 158.0
Sex: All
Minimum age: 4 Years
Maximum age: 6 Years
Healthy volunteers: No

Summary:

      This randomized, double-blind, flexible-dose, placebo-controlled, parallel group study is
      designed to evaluate Aptensio XR® compared to placebo in preschool age children with ADHD.
      Male and female children ages 4 years, 0 months to 5 years, 8 months with a diagnosis of ADHD
      (combined, inattentive or hyperactive/impulsive) will be enrolled.

      There will be 6 phases in this study: a screening phase of up to 4 weeks, which will include
      washout if applicable, an enrollment & parent training phase lasting 2-4 weeks, an
      eligibility phase of up to 2 weeks to determine eligibility for the open-label phase, a
      6-week open-label dose titration phase, a 2 week double-blind phase for Aptensio XR®
      responders, and a two-week follow-up call after study completion or early discontinuation to
      assess for ongoing adverse events and concomitant medications.

      Up to 150 subjects will be enrolled in this trial to allow for subjects who improve
      significantly during the behavior training phase and drop-outs. Once 74 subjects have
      completed the double-blind phase, no additional subjects will be enrolled in the trial.
      Subjects who are already enrolled at that time will be allowed to complete the trial.

      The primary objective of this study is to establish that an optimal dose of Aptensio XR® will
      result in a significant reduction in ADHD symptoms compared with placebo in children ages 4
      to under 6 years.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male and female subjects ages 48 months to 68 months inclusive at time of consent

          2. Met Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5)
             criteria for ADHD, combined, hyperactive/impulsive or inattentive presentation made
             during a clinical interview by an experienced clinician and confirmed with
             Kiddie-Sads-Present and Lifetime Version (K-SADS-PL)

          3. ADHD symptoms must have been present for at least 6 months

          4. Age- and sex-adjusted ratings of ≥ 90th percentile Total Score on the ADHD-RS-IV
             Preschool Version

          5. Score of < 65 on the Child Global Assessment Scale (CGAS)

          6. Must have had a CGI-S score of ≥ 4 at Visit 2 (subjects who were granted a waiver to
             bypass parental training, and did not have a Visit 2, were still qualified to continue
             in the study based on their CGI-S score at screening)

          7. Estimated intelligence quotient (IQ) ≥ 80 on the Kaufman Brief Intelligence Test, 2nd
             edition (KBIT-2). If results from the KBIT-2 were deemed invalid because of
             significant ADHD symptomatology, the PI could submit additional documentation to
             support average cognitive functioning. This documentation could include progress
             reports from preschool or other previous testing. These exceptions were evaluated by
             the Medical Monitor and Study PIs on a case-by-case basis for inclusion.

          8. The subject had a parent or legal guardian who would give written informed consent for
             the subject to participate in the study

          9. Subject and parent or legal guardian must have been able to speak and understand
             English

         10. Subject must live with primary caretaker/rater and have been living with primary
             caretaker for at least 6 months

         11. Subject and parent/guardian must have been willing and able to comply with all
             requirements of the protocol

         12. Systolic and diastolic blood pressure below the 95th percentile for age and gender

        Exclusion Criteria:

          1. The subject had a lack of response to a trial of adequate dose and duration of MPH or
             intolerance to previous methylphenidate (MPH) treatment

          2. The subject was using any other current psychotropic medication except clonidine,
             guanfacine, atomoxetine and/or stimulants or had taken an investigational drug in the
             30 days prior to screening

          3. The subject had used monoamine oxidase inhibitors (MAOIs) within 14 days of the
             screening visit

          4. The subject planned to use prohibited drugs or agents at any point between the
             screening visit and the end of the study

          5. Use of anticonvulsants, antidepressants, or antipsychotics in the 30 days prior to
             screening

          6. The subject should not plan to start any additional psychotherapy outside of the trial
             during the duration of the study

          7. The subject had a history of chronic vocal or motor tics or Tourette's syndrome

          8. The subject had any clinically significant ECG abnormalities at screening

          9. The subject had any major medical conditions that would have interfered with
             involvement in the study or could have been affected negatively by methylphenidate

         10. The subject had chronic medical illnesses including a seizure disorder (excluding a
             history of febrile seizures), severe hypertension, untreated thyroid disease, known
             structural cardiac abnormalities, serious arrhythmias, cardiomyopathy, glaucoma, or a
             family history of sudden death

         11. History (in the past 12 months) or presence of clinically-significant cardiovascular,
             cerebrovascular, renal, hepatic, gastrointestinal, pulmonary, immunological,
             hematological, endocrine, or neurological disease that in the opinion of the
             investigator could have put the subject at risk if he/she participated in the trial or
             which could have confounded study results

         12. Family history (parent or sibling) of structural cardiovascular disease

         13. Current or recent (past 12 months) history of drug abuse in someone living in the
             subject's home

         14. Current symptoms or history of major psychiatric illness (for example schizophrenia,
             psychosis, bipolar disorder, post-traumatic stress disorder, depression, severe
             anxiety disorder, obsessive compulsive disorder or autistic spectrum disorder) in
             addition to ADHD that required treatment with additional medication or, in the opinion
             of the PI, would have contraindicated study participation

         15. History or presence of suicidal ideation or significant self-injurious behavior

         16. The subject showed evidence of current physical, sexual, or emotional abuse

         17. Both biological parents of the subject had a history of bipolar disorder