| Eligibility |
Inclusion Criteria:
1. In Cohort 1, subjects must be at least 4 years old and less than 5 years and 10 months
at Screening; in Cohort 2, subjects must be at least 6 years old and less than 12
years and 10 months at Screening.
2. Subjects must have a body weight within the 5th and 95th percentile according to the
gender-specific weight-for-age percentile charts from the Centers for Disease Control
and Prevention (CDC). See calculator at https://www.infantchart.com/child/.
3. Female subjects must agree, if they are of childbearing potential at Screening or when
they become of childbearing potential during the study, to remain abstinent or agree
to use an effective and medically acceptable form of birth control from the time of
written or verbal assent to at least 14 days after the last dose of study drug.
Childbearing potential is defined as follows: Girls under the age of 12 who have not
had their first period will be considered "not of child-bearing potential." Girls 12
years of age (including girls who will become 13 years during the study) will be
considered "of child-bearing potential," even if they have not yet had their first
period. Irrespective of age, girls who have had their first period, will be considered
"of child-bearing potential."
4. Subjects must be in general good health defined as the absence of any clinically
relevant abnormalities as determined by the Investigator based on physical
examinations, vital signs, electrocardiograms (ECGs), medical history, and clinical
laboratory values (chemistry, hematology, urinalysis) at Screening. If any of the
chemistry or hematology tests are not within the laboratory's reference range, then
the subject can be included only if the Investigator determines the deviations to be
not clinically relevant.
5. At least one parent/legal guardian of the subject must voluntarily give written
permission for him/her to participate in the study.
6. Subjects in Cohort 2 must give written or verbal assent prior to study participation.
For verbal assent, the procedure will be documented and signed by a witness. A parent
or guardian may not be the witness for a child's verbal assent document.
7. Subject must meet Diagnostic and Statistical Manual of Mental Disorders - Fifth
Edition (DSM-5) criteria for a primary diagnosis of ADHD (combined, inattentive, or
hyperactive/impulsive presentation) per clinical evaluation and confirmed by
Mini-International Neuropsychiatric Interview for Children and Adolescents (MINI Kid).
8. Subject has had ADHD symptoms present for at least 6 months prior to the Screening
Visit.
9. Subject must be able and willing to wash out current stimulant ADHD medications,
including herbal medications, from 5 days prior to the start of the Treatment Period,
and abstain from taking these to the end of Visit 6 or ET; and wash out non-stimulant
ADHD medications from 14 days prior to the start of the Treatment Period, and abstain
from taking these to the end of Visit 6.
10. Subject must have a score of =4 (Moderately Ill) on the clinician-administered
Clinical Global Impressions-Severity (CGI-S) scale. For subjects requiring washout of
ADHD medications, this criterion refers to a score following washout.
11. Subjects must have age and sex adjusted ratings of =90th percentile Total Score on the
ADHD-Rating Scale (ADHD-RS) rated over the past 6 months (for 4- and 5-year old
children, use Preschool Version of ADHD-RS-IV; for 6-12 years old children, use
ADHD-RS-5).
12. Subject functions at an age-appropriate level intellectually, as determined by the
Investigator.
13. Subject must have a systolic and diastolic blood pressure below the 95th percentile
for age and gender according to the 2017 AAP guidelines (Flynn 2017) based on the
average of 3 measurements 2-5 minutes apart.
14. Subject, subject's parent/legal guardian, and caregiver (if applicable) must
understand and be willing and able to comply with all study procedures and visit
schedule.
15. Subject, parent/legal guardian, and caregiver (if applicable) must be able to speak
and understand English or Spanish and be able to communicate satisfactorily with the
Investigator and study coordinator.
Exclusion Criteria:
1. If female, must not be pregnant or breastfeeding, and if of childbearing potential,
must have a negative urine pregnancy test at the start of the Screening Period. In
addition, a positive pregnancy test before the last dose of study drug will result in
early termination from the study.
2. Subject with any clinically significant chronic medical condition that, in the
judgment of the Investigator, may interfere with the participant's ability to
participate in the study.
3. Subject has any diagnosis of bipolar I or II disorder, major depressive disorder,
conduct disorder, obsessive-compulsive disorder, any history of psychosis, autism
spectrum disorder, disruptive mood dysregulation disorder (DMDD), intellectual
disability, Tourette's Syndrome, confirmed genetic disorder with cognitive and/or
behavioral disturbances. Subjects with oppositional defiant disorder (ODD) are
permitted to enroll in the study as long as ODD is not the primary focus of treatment,
and, in the opinion of the Investigator, the ODD is mild to moderate, and eligible
subjects with ODD are appropriate and cooperative during Screening.
4. Subject has generalized anxiety disorder or panic disorder that has been the primary
focus of treatment at any time during the 12 months prior to Screening or that has
required pharmacotherapy any time during the 6 months prior to Screening.
5. Subject has evidence of any chronic disease of the central nervous system (CNS) such
as tumors, inflammation, seizure disorder, depression, vascular disorder, potential
CNS-related disorders that might occur in childhood (e.g., Duchenne Muscular
dystrophy, myasthenia gravis, or other neurologic or serious neuromuscular disorders),
or history of persistent neurological symptoms attributable to serious head injury.
6. Subject taking anticonvulsants for seizure control or antidepressants currently or
within the past 2 years before Screening are not eligible for study participation. A
past history of febrile seizure or drug-induced seizure is allowed.
7. Subject has a current (last month) psychiatric diagnosis other than specific phobia,
motor skills disorders, ODD, sleep disorders, elimination disorders, adjustment
disorders, learning disorders, or communication disorders. Subjects allowed to enroll
with any of these DSM disorders will require written justification from the
Investigator documenting why the conditions will not interfere with participation and
to emphasize that ADHD is the primary indication.
8. In the opinion of the Investigator, subject has clinically significant suicidal
ideation/behavior, based on history of attempted suicide and the Columbia-Suicide
Severity Rating Scale (C-SSRS) assessment at Screening.
9. Subject has any clinically significant unstable medical abnormality, chronic disease
(including asthma or diabetes), or a history of a clinically significant abnormality
of the cardiovascular (including cardiomyopathy, serious arrhythmias, structural
cardiac disorders, or severe hypertension), gastrointestinal, respiratory, hepatic, or
renal systems, or a disorder or history of a condition (e.g., malabsorption,
gastrointestinal surgery) that may interfere with absorption, distribution,
metabolism, or excretion of study drug. In cases in which the impact of the condition
upon risk to the subject or study results is unclear, the medical monitor should be
consulted. Any subject with a known cardiovascular disease or condition (even if
controlled) must be discussed with the Medical Monitor during Screening.
10. Subject has a history or presence of abnormal ECGs, which in the Investigator's
opinion is clinically significant.
11. Subject has a history of, or currently has, a malignancy.
12. Subject has uncontrolled thyroid disorder as evidenced by thyroid stimulating hormone
(TSH) =0.8 x the lower limit of normal (LLN) or =1.25 x the upper limit of normal
(ULN) for the reference laboratory at Screening.
13. Subject has greater than trace proteinuria in the urinalysis at Screening. Subjects
with greater than trace proteinuria in the urinalysis at Screening but with a urine
protein to creatinine (UP/C) ratio <0.2 in a first morning void urine sample will not
be excluded from enrollment.
14. Subjects has a current or recent (past 12 months) history of drug abuse; or current or
recent history of drug abuse in someone living in the subject's home, or are using or
planning to use prohibited drugs during the trial as specified in the protocol.
15. Subject has a positive urine drug screen at Screening. Subjects with a positive
methylphenidate (MPH) urine drug screen may be allowed to continue in the study,
provided that the Investigator determines that the positive test is a result of taking
prescribed medications and subject is willing to wash out the current medication as
required.
16. Subject has participated in any other clinical study with an investigational
drug/product within 30 days or at least 5 half-lives, whichever is longer, prior to
Screening.
17. Subject has taken ADHD medications from more than one class within 30 days prior to
Screening. Subjects on a stable dose of one ADHD medication with occasional use of
ADHD medications from another class are eligible at the discretion of the
Investigator.
18. Subjects with demonstrated lack of response or intolerability to adequate dose and
duration of treatment with MPH products. Judgment of adequate dose and duration is at
the discretion of the Investigator.
19. Subject has a positive urine MPH screen by dipstick (e.g., NarcoCheck®) at Visit 2.
20. Subject is planning to initiate psychotherapy during the study (subjects participating
in psychotherapy beginning at least 4 weeks before study initiation are permitted to
continue).
21. Subject has a history of severe allergies or adverse drug reactions to more than one
class of medications.
22. Subject has a history of allergic reaction or a known or suspected sensitivity to MPH
or any substance that is contained in the study drug.
23. Subject, parent/legal guardian, and caregiver (if applicable, at the Investigator's
discretion) has commitments during the study that would interfere with attending study
visits.
24. Subject or subject's family anticipates a move outside the geographic range of the
investigative site during the study period, or plans extended travel inconsistent with
the recommended visit interval during study duration.
25. Subject has one or more siblings living in the same household who are enrolled in this
or another clinical drug trial.
26. Subject shows evidence of current physical, sexual, or emotional abuse.
27. Subject is, in the opinion of the Investigator, unsuitable in any other way to
participate in this study.
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