Please select the eligibility criteria that correspond to the clinical trial below.
Title: Clonidine in Attention Deficit Hyperactivity Disorder (ADHD) Treatment (CAT)
Brief Summary: The purpose of this study is to determine the safety and efficacy of clonidine alone or in combination with methylphenidate for children 7-12 years of age with attention-deficit, hyperactivity disorder.


Options:
A: Inclusion Criteria:

* Male and female subjects aged 6-12 years, inclusive.
* Subjects meeting the DSM-IV criteria for primary diagnosis of ADHD-Combined type, or predominantly hyperactive-impulsive subtype, as established by the K-SADS-PL (Kiddie Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version). If a DSM-IV-defined ADHD diagnosis is difficult to establish due to possible co-morbidity, the subject will not be enrolled into the study.
* Subjects should be on a stabilized total daily dose or nearest equivalent of 40-60 mg methylphenidate or 20-30 mg of d-methylphenidate for at least two weeks prior to Screening visit.

Exclusion Criteria:

* Subject or subject's guardian unable to understand or follow instructions necessary to participate in the study.
* Diagnosed with or history of a tic disorder or Tourette's syndrome.
* History of seizure disorder.
* The presence of a known medical condition that would preclude the use of methylphenidate.
* A history (within the past year) or presence of clinically significant cardiovascular, cerebrovascular, renal, hepatic, gastrointestinal, pulmonary, immunological, hematological, endocrine, or neurological disease.
* ALT (Alanine Amino Transferase), AST (Aspartate Amino Transferase), GGT (Gamma glutamyl transferase) or serum creatinine greater then 2X the ULN (Upper Limit of Normal) at Screening.
* A history of psychiatric illness or substance use disorder (e.g., schizophrenia, bipolar disorder, autism, abuse or dependence, depression, severe Conduct Disorder or severe Oppositional defiant disorder)
* Subjects who have participated in an investigational trial within the past 4 weeks (28 days)
* Subjects who are currently taking antidepressants or other psychotropic medication.
* Subjects who have initiated psychotherapy during the three months prior to randomization.
* Subjects with a positive urine drug screen.
* Subjects who have a history of poor response or intolerance to methylphenidate or d-methylphenidate.

Other protocol-defined inclusion/exclusion criteria may apply
B: Inclusion Criteria:

* Male and female healthy volunteers.
* 18-40 years of age.
* Ability to read and understand English; English can be a second language provided that the participant feels that he/she understand all the questions used in the assessment measures.

Exclusion Criteria:

* Chronic pain condition or chronic or current treatment with any pain medication.
* Presence of any illness or medication use that is judged to interfere with the trial. For example: psychiatric disorder, medication that can influence cognition or emotional processing, i.e. sleep medication, antidepressants, anti-convulsants or opioids.
* Unwillingness to receive brief pain stimulation administered by a heat probe on the hand.
* Allergy or contra-indication to receiving nonsteroidal anti-inflammatory medication and atropine (Treatment with antidepressants, neuroleptics, antihistaminic, levodopa, anti-acids. Pregnancy, breast-feeding, myasthenia gravis, pyloric stenosis, gastro-esophageal reflux, gastric ulcer, constipation, prostatic enlargement, glaucoma, cardio-pulmonary condition -including tachycardia, arrhythmia, arteriosclerosis-, hyperthyroidism, high blood pressure, genetic disease, kidney failure)
C: Inclusion Criteria: Subjects must satisfy the following criteria to be enrolled in the study as an adolescent:

• Male or non-pregnant, non-nursing female at least 12 years of age and less than 18 years of age.

Subjects must satisfy the following criteria to be enrolled in the study as an adult:

• Male or non-pregnant, non-nursing female at least 18 years of age and meeting the local, legal definition of adult.

All subjects must also satisfy the following criteria to be enrolled in the study:

* Confirmation of ADHD diagnosis made at Visit 1 of Study 063-009 or 063-010 (inattentive, hyperactive/impulsive or combined-type, as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition based on clinician assessment using multiple informants and a structured interview).
* Female subjects must be one of the following:
* Surgically sterile prior to screening
* Postmenopausal
* 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 have a negative serum β-hCG pregnancy test, as assessed at Visit 6 of Study 063-009 or 063-010 (data will not be available at the time of entry).
* If the subject is an adult, mentally and physically competent to sign an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. If the subject is an adolescent, 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.

Exclusion Criteria:

* • Having met any exclusion criteria for Study 063-009 or 063-010.

  * Having been diagnosed during Study 063-009 or 063-010 with 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 6 of Study 063-009 or 063-010.
  * Clinically significant ECG abnormalities, as assessed at Visit 6 of Study 063-009 or 063-010 (data will not be available at the time of entry).
  * Clinically significant laboratory abnormalities, as assessed at Visit 6 of Study 063-009 or 063-010 (data will not be available at the time of entry).
  * 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).
  * If the Investigator judges that continued treatment with PRC-063 is not in the subject's best interest.
  * Subjects who are currently considered a suicide risk by the investigator.
  * Having been diagnosed during Study 063-009 or 063-010 with 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.
  * Having been diagnosed during Study 063-009 or 063-010 with physiological dependence (excluding nicotine) on narcotic analgesics or other psychoactive drugs (including barbiturates, opiates, cocaine, cannabinoids, amphetamines and benzodiazepines).
  * Excessive consumption of alcohol occurring during Study 063-009 or 063-010 (consumes alcohol in quantities greater than 15 drinks per week on average; 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).
  * Currently (or within 30 days before the planned start of treatment) receiving an investigational drug or using an experimental medical device, other than PRC-063.
  * Homeless.
D: Inclusion Criteria:

* Children aged 7 through 12 in school.
* All subjects must meet DSM IV criteria for the diagnosis of ADHD of any subtype \[21\].
* Each subject must also satisfy the following criteria regarding the severity of ADHD symptoms: 1. ADHD must be viewed as clinically significant and worthy of treatment by medications as judged by the parent and the site investigator. Operationally, medication treatment will be considered indicated for any subject who has ADHD symptoms that significantly interfere with academic or social functioning and that have not improved (or are not expected to improve) sufficiently with non-pharmacological interventions (e.g., modifying the classroom environment, tutoring). 2. The site investigator's rating of global functioning on the C-GAS must yield a score of 70 or below. Scores below 70 on the C-GAS are designated as indicating abnormal function \[22\]. The score of 70 corresponds to the anchor point description: "Some difficulty in a single area, but generally functioning pretty well."
* Screen of Intelligence using the vocabulary and block design subtests of the Wechsler Intelligence Scale for Children-Third Edition indicates an estimated I.Q \> 70.
* Informed consent/assent signed. We will not enroll any child who does not want to participate.
* The designated school for each subject agrees to participate in the study by completing all required questionnaires and following all specified procedures.
* The child must be able to swallow the tablets and capsules used in this study.

Exclusion Criteria:

* Subjects with tic disorder of any type or tic symptoms, a primary diagnosis of major depression, pervasive developmental disorder, autism, any psychotic disorder, and mental retardation (based on current DSM criteria) will be excluded. We will not exclude subjects with obsessive-compulsive disorder, oppositional-defiant disorder or conduct disorder.
* The presence of a known medical condition that would preclude the use of MPH or clonidine.
* Known pregnancy. A urinary pregnancy test will be performed for all menstruating female subjects. Female subjects of child bearing potential will be advised not to become pregnant. In this circumstance, study medication will be tapered and discontinued and the subject will be terminated from the study. A urinary pregnancy test will be repeated at the end of the study. Subjects who request information regarding possible birth control mechanisms will be referred to their primary care physicians.
* Known presence of impaired renal function. A routine urinalysis will be performed for each subject to exclude signs of renal failure.
* Known active cardiovascular disease/anomaly, which would be a contraindication for the use of MPH or clonidine.
* Subjects may not receive any other medication for the treatment of ADHD. Treatment with MPH or other stimulants must be discontinued for at least 2 weeks prior to enrollment and treatment with other medications to treat ADHD (e.g., antidepressants, clonidine) must be discontinued for at least 6 weeks prior to enrollment.
* Subjects may not receive any other psychotropic medication (e.g., serotonin reuptake inhibitors), anxiolytics (e.g., clonazepam) or hypnotics. Any such medication must be discontinued at least 6 weeks prior to enrollment.
* Previous use of MPH or clonidine will be permitted.

Answer: D