Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-Blind, Placebo-Controlled Study of Mixed Amphetamine Salts (Adderall-XR) for the Treatment of Adult Attention Deficit Hyperactivity Disorder (ADHD) and Cocaine Dependence
Brief Summary: The proposed protocol is a 3 group double-blind, placebo-controlled outpatient study of the safety and efficacy of Adderall-XR (ER-MAS) in the treatment of comorbid ADHD and cocaine dependence. Since this medication has independently shown promise in helping with ADHD and cocaine abuse, we are proposing that it may be successful in the treatment of comorbid ADHD and cocaine abuse. We plan to enroll 75 subjects in a 14-week trial. The primary objectives of the study are to determine the efficacy of ER-MAS in promoting cocaine abstinence and improvement in ADHD symptomology among cocaine-dependent patients with comorbid ADHD.


Options:
A: Inclusion Criteria:

1. Subject must be 18-55 years of age, inclusive at the time of consent.
2. Subject has an established close relationship of at least 6-months duration before screening (Visit -1) with an informant who will be able to observe and be willing to report on the subject's behavior and symptoms in multiple social settings during the course of the study. Informant is defined as a person who has a domicile relationship with the subject. When applicable, the informant should be the subject's spouse/significant other. Additionally, the informant cannot participate as a subject in the study and can only serve as the informant for a single subject.
3. Subject has a lifestyle that in the opinion of the Investigator will enable the subject to complete all study testing and requirements defined in the protocol.
4. Female subjects must have a negative serum beta human chorionic gonadotropin (HCG) pregnancy test at screening (Visit -1) and a negative urine pregnancy test at baseline (Visit 0) and agree to comply with any applicable contraceptive requirements of the protocol.
5. Subject meets the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition - Text Revision (DSM-IV-TR) criteria for a primary diagnosis of ADHD (diagnostic code 314.00 and 314.01) established by a comprehensive psychiatric evaluation that reviews DSM-IV-TR criteria with at least 6 of the 9 subtype criteria met. The Adult ADHD Clinical Diagnostic Scale version 1.2 (ACDS v1.2) will be utilized as the diagnostic tool.
6. Subject has a total score of ≥65 on BRIEF-A GEC T-score by self-report at baseline (Visit 0).
7. Subject has a total score of ≥28 using the Adult ADHD-RS with prompts at baseline (Visit 0).
8. Subject must have a minimum level of intellectual functioning as determined by the Investigator at screening (Visit -1).
9. Subject is able to swallow a capsule.
10. Subject is willing and able to comply with all the testing and requirements defined in this protocol.
11. Subject and informant must be able to provide written, personally signed and dated informed consent to participate in the study in accordance with the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines and applicable regulations before completing any study related procedures.

Exclusion Criteria

1. Subject has a current comorbid psychiatric disorder that is either controlled with medications prohibited in this study or is uncontrolled and associated with significant symptoms. Prohibited disorders include those associated with diagnoses including but not limited to any severe comorbid Axis II disorder or severe Axis I disorder (such as Post Traumatic Stress Disorder \[PTSD\], psychosis, bipolar illness, pervasive developmental disorder, severe obsessive compulsive disorder, severe depressive or severe anxiety disorder). Other symptomatic manifestations (such as agitated states) that contraindicate treatment with SPD489 or confound efficacy or safety assessments in the opinion of the examining physician are also prohibited. Comorbid psychiatric diagnoses will be established by the psychiatric evaluation that includes the Structured Clinical Interview for DSM-IV-TR disorders (SCID-I).
2. Subjects who are currently considered a suicide risk, any subject who has previously made a suicide attempt or those who are currently demonstrating active suicidal ideation.
3. The subject has a body mass index (BMI) of \<18.5 or ≥40.
4. Subject has a concurrent chronic or acute illness (such as severe allergic rhinitis or an infectious process requiring antibiotics), disability, or other condition that might confound the results of safety assessments administered in the study or that might increase risk to the subject. Similarly, the subject will be excluded if he or she has any additional condition(s) that in the Investigator's opinion would prohibit the subject from completing the study or would not be in the best interest of the subject. This would include any significant illness or unstable medical condition that could lead to difficulty complying with the protocol. Mild, stable asthma is not exclusionary.
5. Subject has a history of seizures (other than infantile febrile seizures), any tic disorder, a current diagnosis and/or a known family history of Tourette's Disorder.
6. Subject has known history of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, transient ischemic attack or stroke or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug.
7. Subject has a known family history of sudden cardiac death or ventricular arrhythmia.
8. Subject has any clinically significant ECG or clinically significant laboratory abnormality at screening (Visit -1).
9. Subject has current abnormal thyroid function, defined as abnormal screening thyroid stimulating hormone (TSH) and thyroxine (T4). Treatment with a stable dose of thyroid medication for at least 3 months is permitted.
10. Subject has a history of moderate to severe hypertension or has a resting sitting systolic blood pressure \>139mmHg or diastolic blood pressure \>89mmHg. Subjects with well-controlled mild or moderate hypertension on a single antihypertensive agent are allowed. Combination antihypertensive medications are not allowed.
11. Subject is taking any medication that is excluded.
12. Subject has a documented allergy, hypersensitivity, or intolerance to amphetamines.
13. Subject has a documented allergy, hypersensitivity, or intolerance to any excipients in the investigational medicinal product.
14. Subject has failed to respond to one or more adequate courses (dose and duration) of amphetamine therapy.
15. Subject has a recent history (within the past 6 months) of suspected substance abuse or dependence disorder (excluding nicotine) in accordance with DSM-IV-TR criteria.
16. Subject has a positive urine drug result at screening (Visit -1) (with the exception of subject's current stimulant therapy, if any).
17. Subject has taken an investigational drug or taken part in a clinical trial, including an SPD489 clinical trial, within 30 days prior to screening (Visit -1).
18. Subject has glaucoma.
19. Subject is taking other medications that have central nervous system (CNS) effects or affect performance, such as sedating antihistamines and decongestant sympathomimetics, or are monoamine oxidase inhibitors (during or within 7 days of investigational medicinal product administration). Stable use of bronchodilator inhalers is not exclusionary.
20. Subject is female and pregnant or lactating.
21. Subjects who have previously been randomized into this study and subsequently withdrawn.
22. Subject is well controlled on their current ADHD medication with acceptable tolerability.
B: Inclusion Criteria:

* Male and female outpatients, aged 18-24 years.
* Subjects meeting full criteria for the diagnosis of DSM-IV Attention Deficit Hyperactivity Disorder (ADHD), with onset of symptoms in childhood and persistence of impairing symptoms into adulthood as determined by clinical evaluation and/or ADHD module of structured diagnostic interview, completed by the study clinician.
* Absence of pharmacological treatment for ADHD for the past month.

Exclusion Criteria:

* Any other current psychiatric or medical condition determined to be clinically significant.
* Current use of psychotropics or any medication with clinically significant CNS effects.
* Individuals who have never held a valid driver's license.
* Mental retardation (IQ \< 80).
* Individuals with a history of substance dependence or abuse within the past 6 months. Pregnant or nursing females.
* Known hypersensitivity to Vyvanse or amphetamines.
* Subjects with pre-existing structural cardiac abnormalities.
* Clinically significant abnormal screening values including:
* Laboratory values determined to be clinically significant.
* Consistent readings of hypertension (\>140/90) during screening period (including screening and baseline visits), defined as two or more readings (each being the average of three measurements) at a single visit with systolic blood pressure, SBP \> 140 and/or diastolic blood pressure, DBP, \> 90, and confirmed by manual reading.
* Subjects with isolated incidences (of triplicate average BP) of SBP \> 140 and/or DBP \> 90 at baseline/week 0 visit, confirmed by manual reading, which are determined to be clinically significant.

Subjects with a clinically significant abnormality according to cardiology consultation (ECGs with clinically concerning intervals including PR, QTC, QRS, will be reviewed by cardiology).
C: Inclusion Criteria:

* Must be 18-55 years of age, inclusive.
* Must be male or non-pregnant female. Females of childbearing potential (FOCP) must use contraception.
* Must have a medical assessment with no clinically significant or relevant abnormalities as determined by medical history, PE, clinical and lab evaluation.
* Must have 12-lead ECGs defined by the following parameters:

  1. QT/QTcF interval \< 450 msec for males and \< 470 msec for females
  2. Resting heart rate is between 40 and 100 beats per minute
  3. P-R interval \< 200 msec
  4. QRS interval \<110 msec.
* Meets Diagnostic and Statistical Manual of Mental Disorders Fourth Edition; Text Revision (DSM-IV-TR™) criteria for a primary diagnosis of ADHD (diagnostic code 314.00 and 314.01) established by a psychiatric evaluation that reviews DSM-IV-TR™ criteria with at least 6 of the 9 subtype criteria met. The Adult ADHD Clinical Diagnostic Scale (ACDS v1.2) will be utilized as the diagnostic tool.
* Has a baseline ADHD-RS score greater than or equal to 28 assessed using adult DSM-IV prompts.
* Understands and is able, willing, and likely to fully comply with the study procedures and restrictions.
* Has given written informed consent to participate in the study in accordance with the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines and applicable regulations before completing any study procedures.

Exclusion Criteria:

* In the opinion of the investigator, the subject is significantly underweight \[e.g., Body Mass Index (BMI) \< 18.5\] or morbidly obese.
* Has any comorbid psychiatric diagnosis with significant symptoms such as any severe comorbid Axis II disorders or severe Axis I disorders including Post Traumatic Stress Disorder (PTSD), psychosis, bipolar illness, severe obsessive compulsive disorder, severe depressive or severe anxiety disorder or other symptomatic manifestations that will contraindicate NRP104 treatment or confound efficacy or safety assessments. Specifically, subjects with mild to moderate forms of Axis I disorders including social phobia and dysthymia may be included while subjects with a lifetime history of psychosis or bipolar disorder will be excluded from participation. Comorbid psychiatric diagnoses will be established by a psychiatric evaluation that includes the Structured Clinical Interview for DSM-IV-TR™ disorders (SCID-I) interview at the screening visit.
* Has any concurrent chronic or acute illness or unstable medical condition that could confound the results of safety assessments, increase risk to the subject or lead to difficulty complying with the protocol. Subjects with mental retardation or a severe learning disability are excluded.
* Has a history of seizure (other than infantile febrile seizures), any tic disorder, or a current diagnosis and/or family history of Tourette's Disorder.
* Has a known cardiac structural abnormality or any other condition that may affect cardiac performance.
* Has any clinically significant ECG or laboratory abnormality at Screening or Baseline.
* Subject has a history of hypertension or has a resting sitting systolic blood pressure \> 139mmHg or diastolic blood pressure \> 89mmHg.
* Has used any prohibited medication except for ADHD medications within 30 days of screening visit. Hormonal contraceptives are acceptable.
* Has a documented allergy, intolerance, or documented history of non-responsivity to methylphenidate or amphetamine.
* Currently has (or had a history within the last 6 months of) a drug dependence or substance abuse disorder according to DSM-IV-TR™ criteria (excluding nicotine) as established by a SCID-I at the screening visit.
* Has a positive urine drug result at Screening (with the exception of subject's current stimulant therapy, if any) or at Baseline.
* Has taken an investigational drug or taken part in a clinical trial within 30 days prior to Screening.
* The female subject is pregnant or lactating.
D: Inclusion Criteria:

1. Men and women between the ages of 18-60 who meet DSM-IV criteria for current cocaine dependence and adult ADHD (DSM-IV-TR).
2. Used cocaine at least four days in the past month
3. Must have a Body Mass Index (BMI) \> 18 kg/m2
4. Alcohol Breathalyzer (BraC) at consent of \< 0.04%
5. Individuals must be capable of giving informed consent and capable of complying with study procedures.
6. Women of child bearing age will be included in the study provided that they are not pregnant, based on the results of a blood pregnancy test drawn at the time of screening. They must also agree to use a method of contraception with proven efficacy and agree not to become pregnant during the study. To confirm this, blood pregnancy tests will be repeated monthly. Women will be provided a full explanation of the potential dangers of pregnancy while on the study medication. If a woman becomes pregnant, the study medication will be discontinued.

Exclusion Criteria:

1. Meets DSM-IV-TR criteria for bipolar disorder, schizophrenia or any psychotic disorder other than transient psychosis due to drug abuse.
2. Individuals with any current Axis I psychiatric disorder as defined by DSM-IV-TR supported by the SCID-I/P that in the investigator's judgment are unstable or would be disrupted by study medication or are likely to require pharmacotherapy during the study period.
3. Individuals with current major depressive disorder.However,individuals who are currently stable on a psychotropic medication for three months with a HAM-D \<14 may be included.
4. Individuals physiologically dependent on any other drugs (excluding nicotine or cannabis) which require medical intervention.
5. Individuals with current suicidal risk.
6. Individuals with coronary vascular disease as indicated by history or suspected by abnormal ECG, cardiac symptoms, fainting, open-heart surgery and/or arrhythmia, and family history of ventricular tachycardia/sudden death.
7. Unstable physical disorders which might make participation hazardous such as uncontrolled hypertension (SBP \> 140, DBP\> 90, or HR \> 100 when sitting quietly), acute hepatitis (patients with chronic mildly elevated transaminases \< 3x upper limit of normal are acceptable), or uncontrolled diabetes.
8. Individuals with a history of seizures
9. History of allergic reaction to candidate medication (amphetamine and/or ER-MAS).
10. Women who are pregnant or nursing.
11. History of failure to respond to a previous adequate trial of the candidate medication for cocaine dependence
12. Individuals who are legally mandated (e.g., to avoid incarceration, monetary or other penalties, etc.) to participate in substance abuse treatment program
13. History of glaucoma
14. Individuals who report use of MAOI within 14 days of study start

Answer: D