Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Double-Blind, Placebo-Controlled, Randomized Withdrawal Study of the Safety and Efficacy of Memantine in Pediatric Patients With Autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) Previously Treated With Memantine
Brief Summary: The purpose of this randomized withdrawal study is to evaluate the safety, tolerability, and efficacy of memantine compared with placebo in pediatric patients with autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS).


Options:
A: Inclusion Criteria:

1. Completed at least 12 weeks of exposure to study drug in lead-in study MEM-MD-91 (NCT01592786)
2. Met responder criterion at two consecutive visits separated by at least two weeks in lead-in study MEM-MD-91
3. Provide written informed assent, when developmentally appropriate, to participate in the study before conduct of any study-specific procedures. The parent/guardian/LAR must provide written informed consent before the patient's participation in the study. A separate written informed consent for the caregiver must also be obtained before the conduct of any study specific procedures
4. Have a knowledgeable caregiver who is capable of providing reliable information about the patient's condition, attending all clinic visits with the patient, and overseeing the administration of study drug. Every effort should be made to maintain the same caregiver as used in the lead-in study throughout this study
5. Have normal results from the physical examination, laboratory tests, ECG, and vital signs at Visit 1 of this study (last visit of Study MEM-MD-91). Any abnormal findings must be deemed not clinically significant by the Investigator and documented
6. Be able to speak and understand English sufficiently (or their native language if this can be accommodated by the site), as well as have a caregiver and parent/guardian/LAR who is able to speak and understand English sufficiently (or their native language if this can be accommodated by the site), to comprehend the nature of the study and to allow for the completion of all study assessments
7. Have a family that is sufficiently organized and stable to guarantee adequate safety monitoring and continuous attendance to clinic visits for the duration of the study
8. Females who are 9 years and older or who have had onset of menses must have a negative urine pregnancy test at Visit 1
9. Age of 6 years to 12 years at the time of entry into lead in study MEM-MD-91

Exclusion Criteria:

1. Patients with a concurrent medical condition that might interfere with the conduct of the study, confound interpretation of the study results, or endanger the patient's well being
2. Significant risk of suicidality based on the Investigator's judgment, the Aberrant Behavior Checklist-Irritability subscale (ABC-I), or if appropriate, as indicated by a response of "yes" to questions 4 or 5 in the suicidal ideation section of the Children's C-SSRS (Columbia-Suicide Severity Rating Scale) or any suicidal behavior.
3. Patients with evidence or history of malignancy (other than excised basal cell carcinoma) or any significant hematologic, endocrine, cardiovascular (including any rhythm disorder), neurologic, respiratory, renal, hepatic, or gastrointestinal disease
4. Female patients of child-bearing potential who are not using or not willing to use a conventional method of contraception approved by the PI. Abstinence is an acceptable method of contraception
5. Patients requiring treatment with prohibited concomitant medications
6. Patients who, in the opinion of the Investigator, might not be suitable for the study
7. Employee or immediate relative of an employee of Forest Laboratories, Inc., any of its affiliates or partners, or the study center
B: Inclusion Criteria:

* Meets DSM-IV criteria for autistic disorder, .
* CYBOCS-PDD score of at least 10 at screening.

Exclusion Criteria:

* Diagnosis of Asperger Syndrome or Pervasive Developmental Disorder Not Otherwise Specified, Rett Syndrome, Childhood Disintegrative Disorder.
* Patients planning to commence cognitive behaviour therapy during the period of the study or those who have begun cognitive behaviour therapy within 8 weeks prior to enrolment.
* Patients who are currently taking fluoxetine or who have previously taken it are not eligible for the study.

Other protocol-defined Inclusion/Exclusion criteria may apply.
C: INCLUSION CRITERIA

All Participants:

1. Male and female participants, ages 8-17 years (inclusive)

   Participants with Autism Spectrum Disorder:
2. Meets Diagnostic and Statistical Manual-5 autism spectrum disorder diagnostic criteria, as established by clinical diagnostic interview
3. At least moderate severity of social impairment, as measured by a total raw score of ≥85 on the parent/guardian-completed Social Responsiveness Scale, Second Edition (SRS-2) and a score of ≥4 on the clinician-administered Autism Spectrum Disorder Clinical Global Impression-Severity scale (ASD CGI-S)

Healthy Control Participants:

2. Age-, sex-, and IQ-matched with participants with autism spectrum disorder 3. No Axis I diagnoses, as established by the Kiddie Schedule for Affective Disorders and Schizophrenia-Epidemiological Version (K-SADS-E) and confirmed by clinical diagnostic interview 4. No significant traits of autism spectrum disorder, as measured by a total raw score of \<60 on the parent/guardian-completed Social Responsiveness Scale, Second Edition

EXCLUSION CRITERIA

All Participants:

1. IQ ≤70 based, on the Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II) Vocabulary and Matrix Reasoning subtests
2. Impaired communicative speech
3. Current treatment with the following medications, which are known to impact glutamate levels:

   1. Lamotrigine
   2. Amantadine
   3. N-acetylcysteine
   4. D-cycloserine
4. Current treatment with a psychotropic medication, not listed above, on a dose that has not been stable for at least 4 weeks prior to study baseline
5. Co-administration of drugs that compete with memantine for renal elimination using the same renal cationic system, including hydrochlorothiazide, triamterene, metformin, cimetidine, ranitidine, quinidine, and nicotine
6. Initiation of a new psychosocial intervention within 30 days prior to randomization
7. Participants who are pregnant and/or nursing
8. Participants with a history of non-febrile seizures without a clear and resolved etiology
9. Participants with a history of or a current liver or kidney disease
10. Clinically unstable psychiatric conditions or judged to be at serious suicidal risk
11. Participants who meet for alcohol or drug dependence or abuse on the Kiddie Schedule for Affective Disorders and Schizophrenia-Epidemiological Version. If the participant has a recent history of substance abuse, as an added precaution, there will be a 2-week washout period before initiating the trial. There are no known safety issues relating to memantine and recent history of substance abuse.
12. Serious, stable or unstable, systemic illness, including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease
13. Participants with severe hepatic impairment (Liver Function Tests \[LFTs\] \>3 times the Upper Limit of Normal \[ULN\])
14. Participants with genitourinary conditions that raise urine Power of Hydrogen (pH) (e.g., renal tubular acidosis, severe infection of the urinary tract)
15. Known hypersensitivity to memantine
16. Severe allergies or multiple adverse drug reactions
17. A non-responder or history of intolerance to memantine after treatment at adequate doses, as determined by the clinician
18. Investigator and his/her immediate family, defined as the Investigator's spouse, parent, child, grandparent, or grandchild.
D: Inclusion Criteria:

* Age 18-40
* Able to attend in person therapy sessions in Boston
* Male
* English-speaking
* Normal or corrected vision
* No history of known genetic disorder, significant motor developmental difficulties, prematurity or brain injury
* IQ \> 90, as determined by the WASI
* Score above the cutoff on the Reciprocal Social Interactions and the Restricted, Repetitive, and Stereotyped Behaviors Domains on the ADI-R, meet criteria for PDD or autism on the ADOS, and/or meet DSM-IV criteria for Autism Spectrum Disorder according to clinician interview.

Exclusion Criteria:

* Current use of certain endocrinologically relevant medications
* Current dependence on substances other than tobacco or caffeine
* History of serious medical illness, including neurological, endocrine, cardiac, respiratory, and metabolic diseases that are counter-indications to oxytocin
* Severe, current psychiatric disorder (ie, current mania, severe depression, psychosis, suicidality, severe aggression)
* Long QT, as determined by baseline EKG
* Current participation in other psychotherapy

Additional exclusion criteria for MRI scan only:

Participants who are MRI-ineligible will be enrolled in the clinical trial portion of the study, but will not undergo the MRI scan at MIT. Exclusion criteria for MRI are:

* Presence of metal implants or other metal in the body
* History of claustrophobia or inability to tolerate MRI

Answer: A