Please select the eligibility criteria that correspond to the clinical trial below.
Title: An Evaluation of the Safety and Effectiveness of CONCERTA® (Methylphenidate Hydrochloride), up to 72 mg Daily, in Adolescents With Attention Deficit Hyperactivity Disorder (ADHD)
Brief Summary: The purpose of this study is to evaluate the safety and effectiveness of CONCERTA® (methylphenidate hydrochloride, a central nervous system (CNS) stimulant) versus placebo for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in adolescents..


Options:
A: Inclusion Criteria:

* Diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)
* Children's Global Assessment Scale rating of 41-70 at baseline (Screening Phase)

Exclusion Criteria:

* Subjects who are known to not respond to methylphenidate
* Have had adverse experiences from methylphenidate or hypersensitivity to CONCERTA or its components
* Have marked anxiety, tension or agitation
* Have glaucoma, ongoing seizure disorder, psychotic disorder, Tourette's disorder or family history of Tourette's disorder
B: Inclusion Criteria. Participants for the study must meet all of the following criteria:

1. Consent: The family must provide signature of informed consent by parents or legal guardians.
2. Age at time of Screening: 7 years to 11 years, inclusive
3. Gender: includes male and female children.
4. ADHD Diagnostic Status: ADHD patients must meet DSM-IV criteria for ADHD, Inattentive or Combined subtype. Normal controls must not meet DSM-IV criteria for ADHD, any subtype. Section D.4 below describes in detail the diagnostic process for arriving at diagnosis.
5. Cognitive Functioning: IQ of greater than 80 as estimated by Vocabulary and Block Design subtests of the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV).
6. Learning Disability: All children will be administered the abbreviated WIAT including the Spelling, Reading, and Math subtests. Children must score above 80 on all three WIAT subtests.
7. School: Children must be enrolled in a school setting from which teacher ratings can be obtained.

Exclusion Criteria. Potential participants will be excluded if they meet any of the following criteria:

1. Understanding Level. The patient and parent cannot understand or follow instructions given in the study.
2. History of Psychiatric Medications: Children who have a history of taking any medication for psychological or psychiatric problems will be excluded from participation.
3. Exclusionary Psychiatric Conditions: Children whose primary diagnosis is something other than ADHD will be excluded from participation.
4. Developmental Disabilities. As a result of scores on the IQ screening, additional assessments, or the judgment of the study clinicians, patients will be excluded if they are deemed to be significantly developmentally delayed. This includes clinically significant delays in cognitive function or the presence of other Pervasive Developmental Disorders (PDD).
5. Organic Brain Injury: Children must not have a history of head trauma, neurological disorder, or any other organic disorder that could possibly affect brain function.
C: 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.
D: Inclusion Criteria:

* Must be male or non-pregnant female at least 12 years of age and less than 18 years of age.
* Must have an ADHD diagnosis, in attentive, hyperactive/impulsive or combined, as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) based on clinician assessment using multiple informants and a structured interview.
* Must be unsatisfied with his or her current pharmacological therapy for treatment of ADHD or not currently receiving pharmacological therapy for ADHD. Inclusion of subjects naïve to pharmacological therapy for ADHD is permitted.
* Female subjects must be one of the following: a. surgically sterile prior to screening; b. if of childbearing potential, abstinent or willing to use a reliable method of contraception, such as oral contraceptive, two barrier methods, a barrier method plus a spermicidal agent.
* Female subjects of Child-Bearing Potential (FOCP) must be a negative serum β-hCG pregnancy test at screening.
* Must have a minimum level of intellectual functioning, as determined by an Intelligence Quotient (IQ) score of 80 or above based on the WASI or the KBIT.
* Mentally and physically competent to sign an informed assent document, in the case of the subject, and an informed consent document, in the case of the parent/guardian, indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
* Able and willing to comply with the study procedures for the entire length of the study, including a successful swallow test of an empty 85 mg capsule.
* Total score of 24 or greater on the clinician-rated ADHA-5-RS, as assessed at Visit 2

Exclusion Criteria:

* Having an allergy to methylphenidate or amphetamines or a history of serious adverse reactions to methylphenidate.
* Known to be non-responsive to methylphenidate treatment. Non-response is defined as methylphenidate use at various doses for a phase of at least four weeks at each dose with little or no clinical benefit.
* Being diagnosed with or having a history of strokes, epilepsy, migraine headaches (greater than 1 instance every two months), glaucoma, thyrotoxicosis, tachyarrhythmias or severe angina pectoris or have serious or unstable medical illness. Subjects with controlled or stable asthma or diabetes will be permitted.
* Elevated blood pressure, defined as any values above 89 diastolic or 139 systolic, as assessed at Visit 1.
* Clinically significant ECG abnormalities, as assessed at Visit 1.
* Clinically significant laboratory abnormalities, as assessed at Visit 1.
* Currently receiving guanethidine, pressor agents, MAO inhibitors, coumarin anticoagulants, anticonvulsants (e.g., phenobarbital, phenytoin, primidone), phenylbutazone, tricyclic antidepressants (e.g., imipramine, desipramine), selective serotonin reuptake inhibitors (SSRIs) or herbal remedies (unless on a stable dose for 4 weeks).
* Subject has known history of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary heart disease, transient ischemic attack or stroke or other serious cardiac problems that may place the subject at increased vulnerability to the sympathomimetic effects of a stimulant drug.
* Subject has a known family history of sudden cardiac death or ventricular arrhythmia.
* Subjects who are currently considered a suicide risk by the investigator.
* Having a primary diagnosis of schizophrenia, schizoaffective disorder, primary affective disorder, schizotypal personality, major depression, bipolar disorder, generalized anxiety, borderline personality disorder, antisocial personality or another unstable psychiatric condition requiring treatment, as assessed by the structured interview conducted at Visit 1.
* Having a history or suspected physiological dependence (excluding nicotine) on narcotic analgesics or other psychoactive drugs (including barbiturates, opiates, cocaine, cannabinoids, amphetamines and benzodiazepines).
* Excessive consumption of alcohol (consumes alcohol in quantities greater than 15 drinks per week; 1 drink is defined as 360 mL/12 oz. of beer, 120 mL/4 oz. of wine, or 30 mL/1 oz. of hard liquor), or history (within previous 6 months) of alcohol abuse.
* Currently (or within 30 days before the planned start of treatment) receiving an investigational drug or using an experimental medical device.
* Homeless.

Answer: A