Memantine for the Treatment of Social Deficits in Youth with Disorders of Impaired Social Interactions

Inclusion Criteria:

• Male & female subjects ages 8-18 years (inclusive).

• Diagnostic Statistical Manual (DSM)-5 Autism Spectrum Disorder (ASD) diagnosticcriteria as established by clinical diagnostic interview

• 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)14 and a score of ≥4 on the clinician-administered Clinical GlobalImpression-Severity scale (CGI-S)17.

Exclusion Criteria:

• IQ ≤70 based on the Wechsler Abbreviated Scale of Intelligence-II (WASI-II)Vocabulary and Matrix Reasoning subtests

• Impaired communicative speech

• Subjects currently treated with the following medications (known to impact glutamatelevels): Lamotrigine, Amantadine, N-acetylcysteine, D-cycloserine

• Subjects treated with a psychotropic medication not listed above on a dose that hasnot been stable for at least 4 weeks prior to study baseline.

• Co-administration of drugs that compete with memantine for renal elimination usingthe same renal cationic system, including hydrochlorothiazide, triamterene,metformin, cimetidine, ranitidine, quinidine, and nicotine

• Initiation of a new psychosocial intervention within 30 days prior to randomization.

• Subjects who are pregnant and/or nursing.

• Subjects with a history of non-febrile seizures without a clear and resolvedetiology.

• Subjects with a history of or a current liver or kidney disease.

• Clinically unstable psychiatric conditions or judged to be at serious suicidal risk.

• Subjects who meet on the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-E) for alcohol or drug dependence or abuse. If the subject has a recenthistory of substance abuse, there will be a two-week washout period beforeinitiating the trial as an added precaution. There are no known safety issuesrelating to memantine and recent history of substance abuse.

• Serious, stable or unstable systemic illness including hepatic, renal,gastroenterological, respiratory, cardiovascular (including ischemic heart disease),endocrinologic, neurologic, immunologic, or hematologic disease.

• Subjects with severe hepatic impairment (LFTs > 3 times ULN).

• Subjects with genitourinary conditions that raise urine pH (e.g., renal tubularacidosis, severe infection of the urinary tract).

• Known hypersensitivity to memantine.

• Severe allergies or multiple adverse drug reactions.

• A history of intolerance or adequate exposure to memantine, as determined by theclinician.

• Investigator and his/her immediate family defined as the investigator's spouse,parent, child, grandparent, or grandchild.