Safety and Tolerability Study of Adhansia XR® Extended-Release Capsules in Children
Condition: Attention Deficit/Hyperactivity Disorder
MeSH terms: Attention Deficit Disorder with Hyperactivity
Intervention: Adhansia XR
Intervention description: Methylphenidate extended-release capsules taken once daily (12.5 mg, 25 mg, 35 mg, 45 mg, 55 mg, and 70 mg)
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 103.0
Sex: All
Minimum age: 4 Years
Maximum age: 12 Years
Healthy volunteers: No
Keywords: ADHD; methylphenidate; Adhansia XR; Pediatric

Summary:

      The purpose of this study is to assess the long-term safety of Adhansia XR in children and to
      characterize the pharmacokinetics (PK) in 4 to 5 year-olds.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female subjects ≥4 and ≤12 years of age at the time of informed
             consent/assent.

          -  Females of childbearing potential who are not pregnant and not nursing.

          -  Females of childbearing potential who agree to practice a clinically accepted method
             of contraception during the study and for at least 1 month prior to study dosing and 1
             month following completion of the study. Acceptable contraceptive methods include
             abstinence, oral contraception, surgical sterilization (bilateral tubal ligation,
             bilateral oophorectomy, or hysterectomy), intrauterine device, or diaphragm in
             addition to spermicidal foam and condom on male partner, or systemic contraception
             (eg, levonorgestrel-releasing implant).

          -  Diagnosis of ADHD (any type: combined, predominately hyperactive impulsive type or
             predominately inattentive type) by a psychiatrist, psychologist, pediatrician, or
             licensed allied healthcare professional using the Diagnostic and Statistical Manual of
             Mental Disorders (DSM-5) and confirmed by administration of a structured diagnostic
             interview using the Kiddie-Schedule for Affective Disorders and Schizophrenia for
             School Age Children-Present and Lifetime DSM-5 version (K-SADS-PL).

          -  Subjects who have received, or are receiving treatment with medication (amphetamine,
             methylphenidate, or non-stimulant) for ADHD must be willing to undergo a washout
             period of a minimum of 3 days or 5 half-lives (whichever is longer) prior to study
             drug administration. The washout period for prohibited concomitant medications will be
             at least 5 half-lives or 3 days, whichever is longer.

          -  If subjects are currently off treatment, this must be for any reason other than
             noncompliance, nonresponse, or intolerance to side effects.

          -  Ratings on the attention deficit/hyperactivity disorder-Rating Scale, version 5 (ADHD
             RS-5) when the subject is not receiving treatment for ADHD must be ≥90th percentile
             normative value for sex and age in at least 1 of the categories: total score,
             inattentive subscale, or hyperactive/impulse subscale.

          -  Dissatisfied with his or her current pharmacological therapy for treatment of ADHD or
             not currently receiving pharmacological therapy for ADHD for any reason other than
             nonresponse, noncompliance, or tolerability issues with stimulants. Newly diagnosed
             and treatment naïve subjects may be included at the discretion of the investigator.

          -  Must be functioning at an age-appropriate level intellectually as determined by an
             intelligence quotient (IQ) of ≥80 on a documented IQ assessment such as the Wechsler
             Abbreviated Scale of Intelligence II (WASI-II) vocabulary and matrix reasoning
             components, or the Kaufman Brief Intelligence Test, Second Edition (KBIT-2)

          -  Parent(s)/legal guardian(s) must have the ability to read and understand the language
             in which the informed consent is written and are mentally and physically competent to
             provide written informed consent for their child.

          -  Written or verbal assent from the subject (as applicable).

          -  Subject and parent(s)/legal guardian/caregiver are willing and able to comply with all
             the protocol requirements and parent(s)/legal guardian/caregiver must be able to
             provide transportation for the subject to and from the clinic visits.

        Exclusion Criteria:

          -  Has a known allergy, intolerance, or hypersensitivity to methylphenidate.

          -  History of allergic reactions to tartrazine.

          -  Known nonresponder to methylphenidate treatment.

          -  Subject has received a monoamine oxidase inhibitor within 2 weeks before study
             treatment.

          -  Blood pressure and heart rate outside the 95th percentile for age and sex.

          -  Subject has a current or recent history (within the past 6 months) of drug abuse or
             dependence disorder; or someone in the subject's immediate family has a current or
             recent history (within the past 6 months) of drug abuse or dependence disorder; or
             someone living at the subject's home has a current or recent history (within the past
             6 months) of drug abuse or dependence disorder; or subject has a positive urine drug
             screen for stimulant medication (other than currently prescribed stimulant for the
             treatment of ADHD) or drugs of abuse at the screening visit.

          -  Has abnormal thyroid function, glaucoma, Gilles de la Tourette's disorder, a history
             of seizures (except simple febrile seizures), or a tic disorder. Mild medication
             induced tics are not exclusionary.

          -  Primary and/or comorbid psychiatric diagnosis other than ADHD with the exception of
             simple phobias, motor skill disorders, communication disorders, learning disorders,
             and adjustment disorders so long as such disorder is judged not to interfere with
             study participation or the safety of the subject.

          -  Subjects with a family history (first-degree relatives) of sudden cardiac death
             require review and approval by the medical monitor for participation in the study.

          -  Subject has a history of disorders of the sensory organs, including deafness,
             blindness or the subject is severely or profoundly developmentally disabled.

          -  Any clinically significant abnormality or clinically significant abnormal laboratory
             test results found during screening or a positive test for hepatitis A, hepatitis B,
             hepatitis C, or HIV found during screening (subjects who have received a hepatitis A
             vaccine and test positive for hepatitis A may be included in the study, at the
             discretion of the investigator).

          -  Use of an investigational drug within 30 days (90 days for biologics) or participation
             in an investigational study within 30 days prior to dosing.

          -  Any reason which, in the opinion of the investigator, would prevent the subject from
             participating in the study.

          -  Clinically significant ECG abnormalities (including but not limited to Wolff
             Parkinson-White syndrome, supraventricular tachycardia, left ventricular hypertrophy,
             abnormal conduction defect, or other cardiac arrhythmia), or vital sign abnormalities
             (normal vital signs should be between 5th and 95th percentile for age) at screening.

          -  Known history of cardiovascular disorders including hypertension, angina, arterial
             occlusive disease, heart failure, hemodynamically significant congenital heart
             disease, cardiomyopathies, myocardial infarction, potentially life-threatening
             arrhythmias, and channelopathies (disorders caused by the dysfunction of ion
             channels).

          -  Clinically significant history of neurological, endocrinal (including thyrotoxicosis),
             pulmonary, hematological, immunologic, gastrointestinal, renal, hepatic or metabolic
             disease, or psychiatric illness other than ADHD.

          -  History of anxiety, tension, agitation, motor tics, Tourette's syndrome or a family
             history (first-degree relatives) of Tourette's syndrome.

          -  History of glaucoma.

          -  Has a positive serum pregnancy test (if applicable) at screening.

          -  Positive findings on the Columbia-Suicide Severity Rating Scale (C-SSRS) for suicidal
             ideation or behaviors at screening.

          -  Clinically significant illness or surgery within 4 weeks prior to dosing. Subjects who
             experience vomiting within 24 hours prior to clinic admission will be carefully
             evaluated for upcoming illness/disease.

          -  Hemoglobin <105 g/L or hematocrit <0.310 L/L at screening (subjects with abnormal
             hemoglobin and/or hematocrit levels deemed not clinically significant may be included
             in the study, at the discretion of the investigator).

          -  Subject has received anticonvulsants (eg, phenobarbital, phenytoin, primidone),
             coumarin anticoagulants, prescription pressor agents, pressor agents, guanethidine,
             tricyclic antidepressants (imipramine, desipramine, selective serotonin inhibitors) or
             herbal remedies within 30 days prior to the first dosing, or melatonin within 3 days
             prior to the first dosing.

        Other protocol specific inclusion/exclusion criteria may apply.