A Pivotal Efficacy Trial to Evaluate HLD200 in Children With ADHD in a Naturalistic Setting
Condition: Attention Deficit Hyperactivity Disorder
MeSH terms: Attention Deficit Disorder with Hyperactivity
Intervention: HLD200 methylphenidate hydrochloride (MPH) Capsules; Placebo
Intervention description: HLD200 Doses: 40, 60 or 80 mg
Intervention MeSH terms: Methylphenidate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 163.0
Sex: All
Minimum age: 6 Years
Maximum age: 12 Years
Healthy volunteers: No

Summary:

      This Phase 3 pivotal efficacy trial will examine the effects of HLD200 (methylphenidate) in
      patients aged 6-12 years with ADHD in a naturalistic setting. Following a screening/washout
      period (Visit 1), subjects will randomized to double-blind placebo or HLD200 for a period of
      3 weeks (Visits 2-5) before assessing clinical study endpoints at last study visit.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subjects must be male or female children (6 to 12 years at the time of consent).

          2. Subjects must have a diagnosis of ADHD as defined by DSM5 criteria and confirmation
             using the Mini International Neuropsychiatric Interview for Children and Adolescents
             (MINI-KID).

          3. Subjects must have a baseline ADHD-RS-IV score at or above the 90th percentile
             normalized for sex and age in total score. In addition, this ADHD-RS-IV total score
             must be ≥26 at Baseline.

          4. Subjects must have a Clinical Global Impression of Severity (CGI-S) score ≥4 and a
             CGI-P score >10 at the Baseline Visit.

          5. Subjects have demonstrated, in the judgment of the investigator, at least a partial
             clinical response to MPH.

          6. Parental or legal guardian confirmation of the child's before-school functional
             impairment and/or difficulties performing a morning routine of at least 30 minutes
             minimum duration occurring between 6:00 and 9:00 am.

          7. Subject body weight must be ≥20 kg.

          8. Subject must be considered clinically appropriate for treatment with MPH and HLD200,
             including ability to swallow treatment capsules.

          9. Subject must be in general good health based upon the medical history, physical, and
             laboratory examinations (including urine drug screen).

         10. Subject and parent or legal guardian must be able to read, write, and/or understand at
             a level sufficient to provide informed consent (parent/legal guardian) and assent
             (subject) prior to study participation and to complete study-related materials.
             Subject and parent or legal guardian must plan to be available for the entire study
             period.

         11. Female subjects of childbearing potential (i.e., post-menarche) are required to have a
             negative result on urine pregnancy testing at screening (and will be given specific
             instructions for avoiding pregnancy during the study).

         12. A medically highly effective form of birth control must be used during the study and
             for 90 days thereafter for subjects of either sex of childbearing potential. Examples
             of medically highly effective forms of birth control are as follows:

               -  No sexual activity

               -  Use of acceptable methods of birth control including intra-uterine device, oral,
                  implantable,or injectable contraceptives.

        Exclusion Criteria:

          1. History of, or current, medical condition or laboratory result which, in the opinion
             of the investigator, unfavorably alters the risk-benefit of study participation, may
             jeopardize subject safety, or may interfere with the satisfactory completion of the
             study and study-related procedures.

          2. Serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm
             abnormalities, or other cardiac problems that may place the subject at increased
             vulnerability to the sympathomimetic effects of a stimulant drug.

          3. History of seizure disorder (except febrile seizures prior to age 5 and with last
             occurrence at least 1 year prior to study participation), Tourette's disorder, or
             intellectual disability of minor severity or greater (DSM5 criteria).

          4. History of psychosis, bipolar disorder, anorexia nervosa, bulimia, or suicide attempt.
             Current depression, anxiety, conduct/behavior disorder, substance use disorder, or
             other psychiatric condition which, in the investigator's opinion, may jeopardize
             subject safety or may interfere with the satisfactory completion of the study and
             study-related procedures.

          5. Active suicidal ideation as evidenced by an ideation score of 2 or greater on the
             C-SSRS.

          6. History of severe allergic reaction or intolerance to MPH.

          7. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, or
             creatinine greater than 1.5x the upper limit of normal. Elevated bilirubin due only to
             Gilbert's syndrome is not exclusionary.

          8. History of alcohol abuse or illicit drug use.

          9. Use of prescription medications (except per protocol allowed medications) within 7
             days of Baseline (Visit 2), except for ADHD stimulant medication (72 hours) and
             monoamine oxidase inhibitors (MAOIs) (14 days), and over-the-counter medications
             (except birth control and allowed medications) within the 3 days preceding Baseline
             (Visit 2). Medications not covered in allowed medications or prohibited medications
             must be cleared by the medical monitor prior to enrolling the subject.

         10. Use of psychotropic medications including antidepressants, mood stabilizers, and
             antipsychotics.

         11. Participation in a clinical trial with an investigational drug within the 30 days
             preceding study enrollment.

         12. Previous treatment experience with HLD200.

         13. Positive screening for illicit drug use or nicotine and/or current health conditions
             or use of medications that might confound the results of the study or increase risk to
             the subject.

         14. In the opinion of the investigator, the subject may have problems complying with the
             protocol or the procedures of the protocol, or for which the study could pose
             unnecessary safety risks. This includes current health conditions or use of
             medications that might confound the results of the study or increase risk to the
             subject.

         15. A sibling or step-sibling that is concurrently participating in this study who resides
             with and is cared for by the same parent/legal guardian as the subject.