Please select the eligibility criteria that correspond to the clinical trial below.
Title: Intranasal Oxytocin in the Treatment of Autism
Brief Summary: The purpose of this study is to learn whether or not the drug called oxytocin is helpful in improving mood and social functioning in adults with autism.


Options:
A: Inclusion Criteria:

* Males and females between the ages of 5 and 17 years 2 months.
* Weight of 15 kg or greater.
* DSM-IV diagnosis of Autistic Disorder.
* Inpatient or outpatient.
* Medication free for at least 2 weeks for all psychotropic medications (4 weeks for fluoxetine or depot neuroleptics).
* Anticonvulsants used for treatment of seizure disorder permitted if the dosage has been stable for 4 weeks and patient seizure free for at least 6 months.
* Clinical Global Impression Severity score of at least 4 and a)18 or greater on the Irritability Scale of the Aberrant Behavior Checklist or b) .5 total score on the Ritvo-Freeman scale.
* Mental age of at least 18 months.
* Negative pregnancy test

Exclusion Criteria:

* IQ below 18 months.
* Females with a positive pregnancy test. - Evidence of a prior adequate trial with risperidone.
* Evidence of hypersensitivity to risperidone.
* Past history of neuroleptic malignant syndrome.
* DSM-IV diagnosis of Pervasive Developmental Disorder other than Autistic Disorder.
* Significant medical condition such as heart disease, hypertension, liver or renal failure, pulmonary disease, or unstable seizure disorder.
* Weight less than 15 kg.
B: Inclusion Criteria:

* Be between the ages of 3 years 0 months and 17 years 11 months at the time of randomization
* Be diagnosed by clinician experienced in assessment of ASD with autistic disorder, Asperger's syndrome, or PDD-NOS using DSM-V-TR criteria
* Must have clinical diagnosis of ASD confirmed using the Autism Diagnostic Observation Scale (ADOS, Lord et al., 2001)
* Must have clinical diagnosis of ASD confirmed using the Autism Diagnostic Interview-Revised (ADI-R, Rutter, 2003). ASD criteria proposed by Risi (2006). Specifically, subject must be within 1 point of autism criteria on both social and communication domains of the ADI or meet autism criteria in one of these ADI domains and come within 2 points of autism criteria in the other
* Have a guardian who is able to provide informed consent
* If cognitively able, subject must be able to provide informed assent/consent

Exclusion Criteria:

* Have a known diagnosis of Rett Syndrome or Childhood Disintegrative Disorder, or have marked sensory impairment such as deafness or blindness
* Have active cardiovascular disease or renal disease that is not controlled by medication
* Subjects who are pregnant, lactating, or who refuse to practice contraception if sexually active
* Subjects who have had changes in allied health therapies, behavioral or educational interventions within the two months prior to randomization other than those associated with school holidays
* Subjects who have had changes in psychiatric medications within 4 weeks of randomization
* Subjects who have had previous chronic treatment with oxytocin
* Subjects who have caretakers who are unable to speak English, be consistently present at visits to report on symptoms, or are otherwise judged as unable to comply with the protocol by the data collection site team
* Subjects with active seizures within the 6 months preceding screening or baseline -added part way through study in response to subject death.
C: Inclusion Criteria:

1. Male or female outpatients 18 to 60 years of age.
2. Meet Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. The diagnosis will be confirmed with Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule .
3. Have a Clinician's Global Impression-Severity score ≥ 4 (moderately ill) at Screening and Baseline.
4. If already receiving stable nonpharmacologic educational, behavioral, and/or dietary interventions, have continuous participation during the preceding 3 months prior to Screening and will not electively initiate new or modify ongoing interventions for the duration of the study.
5. Have normal physical examination and laboratory test results at Screening. If abnormal, the finding(s) must be deemed clinically insignificant by the Investigators.
6. The patient must be able to speak and understand English sufficiently to understand the nature of the study and to allow for the completion of all study assessments.
7. Have a normal Intelligence Quotient (\>70) supported by the Wechsler Abbreviated Scales of Intelligence.

Exclusion Criteria:

1. Patients born prior to 35 weeks gestational age.
2. Patients with any primary psychiatric diagnosis other than autism at Screening: a history of attention deficit hyperactivity disorder, bipolar disorder, psychosis, posttraumatic stress disorder, schizophrenia, or major depressive disorder.
3. Patients with a medical history of neurological disease, including, but not limited to, epilepsy/seizure disorder (except simple febrile seizures), movement disorder, tuberous sclerosis, fragile X, and any other known genetic syndromes, or known abnormal magnetic resonance imaging/structural lesion of the brain.
4. Pregnant female patients.
5. Patients with a medical condition that might interfere with the conduct of the study, confound interpretation of the study results, or endanger their own well-being. Patients with evidence or history of malignancy or any significant hematological, endocrine, cardiovascular (including any rhythm disorder), respiratory, renal, hepatic, or gastrointestinal disease.
6. Patients taking psychoactive medication(s) (e.g., stimulants, antidepressants, antipsychotics, antiepileptics, anxiolytics, clonidine).
7. Patients who plan to initiate or change nonpharmacologic interventions during the course of the study.
8. Patients unable to tolerate venipuncture procedures for blood sampling.
9. Patients who, in the Investigator's opinion, might not be suitable for the study.
D: Inclusion Criteria:

* Written informed consent from parent(s) or legal guardian(s) with sufficient intellectual capacity to understand the study and support subjects' adherence to the study procedures must be obtained for subjects who are not emancipated. In accordance with Institutional Review Board (IRB) requirements, the subject will complete an informed assent when developmentally appropriate, to participate in the study before conduct of any study-specific procedures.
* Male or female subjects 6 to 17 years of age, inclusive, at the time of consent.
* A reliable informant (eg, parent, legal guardian, or caregiver) who has past and current direct knowledge of the subject must accompany the subject at each visit and must oversee the administration of the study drug.
* DSM-IV-TR primary diagnosis of autistic disorder confirmation of the diagnosis by a trained clinician (eg, psychiatrist, psychologist, social workers, etc) at the time of screening, by means of the Autism Diagnostic Interview, Revised (ADI-R).
* Screening and Baseline ABC irritability subscale score ≥ 18.
* Screening and Baseline CGI-S ≥ 4.
* Within 5th to 95th percentile for gender specific Growth Charts from Centers for Disease Control (CDC).
* No clinically relevant abnormal laboratory values.
* No clinically relevant abnormal vital sign values/findings

  1. Females who participate in this study:

     * are unable to become pregnant (eg, premenarchal, surgically sterile, etc.) -OR-
     * practices true abstinence (consistent with lifestyle) and must agree to remain abstinent from signing informed consent to at least 7 days after the last dose of study drug has been taken;

-OR-

•are sexually active and willing to use a medically effective method of birth control (eg, male using condom and female using condom, diaphragm, contraceptive sponge, spermicide, contraceptive pill, or intrauterine device) from signing informed consent to at least 7 days after the last dose of study drug has been taken.

* Males must be willing to remain sexually abstinent (consistent with lifestyle) or use an effective method of birth control (eg, male using condom and female using condom, diaphragm, contraceptive sponge, spermicide, contraceptive pill, or intrauterine device) from signing informed consent to at least 7 days after the last dose of study drug has been taken.
* In the judgment of the investigator, the subject is able to swallow the size and number of study drug tablets specified per protocol (See Table 4 for study drug tablet size).
* Able to adhere to protocol-specified meal requirements during dosing.
* Have a stable living arrangement for at least 3 months prior to screening.
* Non-pharmacologic therapy (eg, behavior modification) must be stable for at least 4 weeks before screening and consistent throughout the study.

Exclusion Criteria:

* Subjects with profound intellectual disability.
* Current diagnosis of bipolar disorder, psychosis, schizophrenia or major depression, or childhood disintegrative disorder as confirmed by the MINI-Kid (as appropriate) at screening. Confirmed genetic disorders with cognitive and behavioral disturbances are also exclusionary.
* Clinically significant neurological, metabolic (including type 1 and type 2 diabetes), hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, carcinoma, and/or urological disorder that would pose a risk to the subjects if they were to participate in the study or that might confound the results of the study.

Note: Active medical conditions that are minor or well-controlled are not exclusionary if they do not affect risk to the subject or the study results. In cases in which the impact of the condition upon risk to the subject or study results is unclear, the Medical Monitor should be consulted. Any subject with a known cardiovascular disease or condition (even if controlled) must be discussed with the Medical Monitor during screening.

* Evidence of any chronic organic disease of the CNS such as tumors, inflammation, active seizure disorder, vascular disorder, potential CNS related disorders that might occur in childhood- eg, Duchenne Muscular dystrophy, myasthenia gravis, or other neurologic or serious neuromuscular disorders. In addition, subjects must not have a history of persistent neurological symptoms attributable to serious head injury. Past history of febrile seizure, drug-induced seizure, or alcohol withdrawal seizure is not exclusionary.
* If the subject has a history of seizures, the subjects must not currently be taking any antiepileptic drugs (AEDs) and be seizure-free for at least 6 months.
* Clinically significant finding(s) on physical examination determined by the investigator to pose a health concern to the subject while on study.
* A history or presence of abnormal ECG, which in the investigator's opinion is clinically significant. Screening ECGs will be centrally over-read, and eligibility will be determined based on the over-read.
* Known history or presence of clinically significant intolerance to any antipsychotic medications including but not limited to angioedema, serotonin or neuroleptic malignant syndromes, severe dystonia, or moderate to severe tardive dyskinesia.
* Clinically significant alcohol abuse/dependence or drug abuse/dependence based on Mini International Neuropsychiatric Interview for children and adolescents (MINI-Kid) criteria within the last 6 months prior to screening.
* Clinically significant orthostatic hypotension (ie, a drop in systolic blood pressure of 20 mmHg or more and/or drop in diastolic blood pressure of 10 mmHg or more within 4 minutes of standing up).
* Presence or history (within the last year) of a medical or surgical condition (eg, gastrointestinal disease) that might interfere with the absorption, metabolism, or excretion of orally administered lurasidone.
* Positive test results at screening for:

  1. Urine drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine, opiates, phencyclidine, cannabinoids, methamphetamine, and methadone). However, a positive test for amphetamines, barbiturates, opiates, benzodiazepines or methadone may not result in exclusion of subjects if the investigator determines that the positive test is as a result of prescription medicine(s).
  2. Pregnancy test (only in female subjects ≥ 11 years old).
* Lifetime history of human immunodeficiency virus (HIV) positive or acquired immune deficiency syndrome (AIDS), or history of Hepatitis B or C.
* Participated in another interventional clinical trial or receiving an investigational product within 30 days prior to study drug administration.
* Use of concomitant medications that consistently prolong the QT/QTc interval within 28 days prior to randomization.
* Received depot neuroleptics unless the last injection was at least 1 month or 1 treatment cycle prior to screening, whichever is longer.
* Subject has received treatment with antidepressants within 3 days, fluoxetine hydrochloride at any time within 21 days, an MAO inhibitor within 21 days of randomization or clozapine within 120 days of randomization. Depot neuroleptics must be discontinued at least one treatment cycle prior to randomization.
* Use of any antipsychotic medication (other than study drug), carbamazepine, oxcarbazepine or fluvoxamine, within 3 days prior to randomization.
* Females who are pregnant, lactating, or likely to become pregnant during the study.
* Donation of whole blood within 60 days prior to randomization.
* Has a prolactin concentration greater than or equal to 100 ng/mL at screening.
* Subject is considered by the investigator to be at imminent risk of suicide during the study. Subject has a history of one or more serious suicide attempts (based on the investigator's judgment) in the 12 months prior to screening. Subjects determined to be at risk of suicide or injury, as assessed by the investigator at screening, will be referred for further psychiatric evaluation.
* Clinically relevant history of drug hypersensitivity to lurasidone or any components in the formulation.
* Subject requires use of concomitant medications that are potent inducers or inhibitors of the cytochrome P450 (CYP) 3A4 enzyme system (Appendix C) from signing informed consent until follow-up.

Answer: C