Please select the eligibility criteria that correspond to the clinical trial below.
Title: The ABC Study: A Double-Blind, Randomized, Placebo-Controlled, Crossover Study Evaluating the Academic, Behavioral, and Cognitive Effects of CONCERTA on Older Children With ADHD
Brief Summary: The purpose of this trial is to determine if the study medication, CONCERTA (methylphenidate HCl), is safe and effective in improving academic performance and behavior in children with attention deficit hyperactivity disorder (ADHD), when compared to placebo.


Options:
A: Inclusion Criteria:

* ADHD diagnosis of all subtypes (except Not Otherwise Specified)
* Patients with total or subscale Attention Deficit Hyperactivity Disorder Rating Scale (ADHD RS-IV) scores \> =90th percentile relative to the general population of children by age and gender
* Patients currently receiving ADHD medication must be inadequately managed on their current stimulant dose and meet this criteria at the screening visit
* Ability to read and understand English
* Ability to attend school regularly.

Exclusion Criteria:

* Estimated Full Scale IQ score of 80 or below
* Severe Learning Disability
* History of, or current, primary diagnosis of: severe anxiety disorder, conduct disorder, psychotic disorders, pervasive developmental disorder, eating disorder, obsessive-compulsive disorder, sleep disorder, major depressive disorder, bipolar disorder, substance use disorder, chronic tic disorder, personal or family history of Tourette's syndrome
* Weight \< 3rd percentile for age
* History of hospitalization for treatment of a mood, anxiety, or psychotic disorder
* History of failed response to methylphenidate.
B: 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 at least 1 of the following categories: 1) Hyperactive Impulse; 2) Inattentive; or 3) Total Score. In addition, this ADHD-RS-IV Total Score must be greater or equal to 26.
4. Subjects must have a Clinical Global Impression of Severity (CGI-S) score greater than or equal to 4 and a CGI-P score \>10 at the Baseline Visit.
5. Subjects who are not currently on MPH treatment must either 1) have prior experience with MPH treatment and have shown clinical response to therapy during that time; or 2) be treated with the same dose of MPH and show a clinical response with acceptable tolerability to MPH for ≥2 weeks prior to screening.
6. Parental or legal guardian confirmation of before-school function impairment and difficulties performing morning routine.
7. Regular weekday morning routine of no less than 30 minutes.
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 medical history, physical examination, and laboratory results (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 a parent/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 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 to MPH.
7. History of no response or intolerance to the adverse effects of MPH;
8. 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.
9. History of alcohol abuse or illicit drug use.
10. Use of prescription medications (except allowed medications; see Section 8.1.2) within 7 days of Baseline (Visit 2), except for ADHD stimulant medication (5 days) 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 (Section 8.1.1) must be cleared by the medical monitor prior to enrolling the subject.
11. Participation in a clinical study 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 could face unnecessary safety risks from the study. This includes current health conditions or use of medications that might confound the results of the study or increase risk to the subject.
15. Subject's systolic or diastolic blood pressure measurement exceeds the 95th percentile for age, sex, and height at the Baseline visit.
16. Subject is significantly underweight based on Centers for Disease Control and Prevention body mass index (BMI)-for-age sex-specific values at the Screening Visit. Significantly underweight is defined as a BMI \<5th percentile.
17. Subject is significantly overweight based on Centers for Disease Control and Prevention BMI-for-age sex specific values at the Screening Visit. Significantly overweight is defined as a BMI \>95th percentile.
C: Inclusion Criteria:

* Subject must be 13-17 years of age, inclusive, at the time of consent.
* Subject must weigh more than 79.5lb.
* The parent/LAR must be available at approximately 7:00AM (±2 hours) to dispense the dose of investigational product for the study duration.
* Subject, who is a female, must have a negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test and a negative urine pregnancy test and agree to comply with any applicable contraceptive requirements of the protocol.
* Subject has an ADHD-RS-IV total score ≥28.
* Subject is able to swallow a capsule.
* Subject does not have hypertension and has a resting sitting blood pressure less than or equal to 135/85mmHg.

Exclusion Criteria

* Subject has a current, controlled (with medications prohibited in this study) or uncontrolled, comorbid psychiatric diagnosis with significant symptoms such as any significant comorbid Axis II disorder or significant Axis I disorder (such as post traumatic stress disorder, psychosis, bipolar illness, pervasive developmental disorder, severe obsessive compulsive disorder, depressive or anxiety disorder.
* Diagnosis of conduct disorder. Oppositional defiant disorder is not exclusionary.
* Subject is considered a suicide risk, has previously made a suicide attempt, or is currently demonstrating active suicidal ideation. Subjects with intermittent passive suicidal ideation are not necessarily excluded.
* Subject is underweight or overweight.
* Subject has a concurrent chronic or acute illness (such as severe allergic rhinitis or an infectious process requiring antibiotics), disability, or other condition. Mild, stable asthma is not exclusionary.
* Subject has a history of seizures (other than infantile febrile seizures), a chronic or current tic disorder, or a current diagnosis and/or a known family history of Tourette's Disorder.
* Subject has a known history of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems that may place him/her at increased vulnerability to the sympathomimetic effects of a stimulant medication.
* Subject has a known family history of sudden cardiac death or ventricular arrhythmia.
* Subject has any clinically significant ECG or clinically significant laboratory abnormality.
* Subject has current abnormal thyroid function, defined as abnormal thyroid stimulating hormone (TSH) and thyroxine (T4). Treatment with a stable dose of thyroid medication for at least 3 months is permitted.
* Subject has a documented allergy, hypersensitivity, or intolerance to amphetamine or to any excipients in the investigational product.
* Subject has a documented allergy, hypersensitivity, or intolerance to MPH or to any excipients in the reference product.
* Subject has failed to fully respond to an adequate course(s) (dose and duration) of MPH or amphetamine therapy.
* Subject has a history of suspected substance abuse or dependence disorder (excluding nicotine). Subjects with a lifetime history of amphetamine, cocaine, or other stimulant abuse and/or dependence will be excluded.
* Subject has a positive urine drug result.
* Subject has previously participated in this study or another clinical study involving SPD489/NRP104.
* Subject has glaucoma.
* Subject is required to take or anticipates the need to take medications that have CNS effects or affect performance, such as sedating antihistamines and decongestant sympathomimetics, or are monoamine oxidase inhibitors. Stable use of bronchodilator inhalers is not exclusionary.
* Subject is female and is pregnant or lactating.
* Subject is well controlled on his/her current ADHD medication.
* Subject has a pre-existing severe gastrointestinal tract narrowing.
D: Inclusion Criteria:

* The patient is between 6-12 years old (both inclusive).
* The patient satisfies the DSM-IV criteria for ADHD or ADD.
* The patient has a responsible caregiver who is able to provide information about the patient's functional status.
* Written informed consent is obtained from the patient and the legally accepted representative.

Exclusion Criteria:

* The patient does satisfy the DSM-IV for autism spectrum disorder.
* The patient does have situational hyperactivity, pervasive developmental disorders, schizophrenia, other psychotic disorders such as mood or anxiety disorder, personality disorder as unsocial behaviour, personality change due to a general medical condition, mental retardation (IQ \< 70), understimulating environments, conduct disorder, chorea and other dyskinesias. The patient does not have tics or Tourette's syndrome, or personal or family history of psychotic disorder, bipolar illness, depression, or suicide attempt.
* The patient does have any chronic medical disorder (diabetes, epilepsy or other seizure disorder, autoimmune disorder, gastrointestinal disorder, renal or cardiovascular disorders, etc.) or acute inflammatory disease. The patient does not have glaucoma, heart disease, heart rhythm disorder, high blood pressure, or peripheral vascular disease such as Raynaud's syndrome.
* The patient did use any of these medications during the 3 months before entering the study: clonidine, guanethidine, blood thinners (e.g. warfarin or Coumadin), antidepressants (e.g. amitriptyline, citalopram, doxepin, fluoxetine, nortriptyline, paroxetine, sertraline), cold or allergy medicine that contains a decongestant, medications to treat high or low blood pressure, seizure medicine (e.g. phenobarbital, phenytoin, primidone), or diet pills.
* The patient did take MAO inhibitor (isocarboxazid, linezolid, phenelzine, rasagiline, selegiline or tranylcypromine) in the past 14 days.
* The patient has any other contraindication for the use of methylphenidate.
* The patient did use vitamin/mineral/herbal/omega-3 supplements or other any medication (psychoactive medication, antibiotics, anti-inflammatory drugs, melatonin, etc.) \> 1 week during the 3 months before inclusion.

Answer: A