Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase II Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety, and Tolerability of Arbaclofen Administered for the Treatment of Social Function in Children and Adolescents With Autism Spectrum Disorders
Brief Summary: AIMS-2-CT-01 is a randomized, double-blind, placebo controlled, study to explore the efficacy, safety and tolerability of Arbaclofen administered to children and adolescents (ages 5-17) for the treatment of social adaptive function in participants with ASD. The effects of Arbaclofen on social function in children and adolescents with ASD will be evaluated in a randomized, placebo controlled, parallel-group study of 16 weeks duration. Subjects who meet protocol criteria will be randomly allocated to receive either Arbaclofen or placebo in a 1:1 ratio in the Treatment Period. There will be 7 recruiting sites and randomization will be stratified by site. A sample of 130 patients will be recruited. Blinding will be maintained by utilizing identical tablets containing either Arbaclofen or placebo.


Options:
A: Inclusion Criteria:

* Age 3 Years to 12 Years
* Diagnostic Statistical Manual Version -IV (DSM-IV) and Autism Diagnostic Interview - Revised (ADI-R)-confirmed Diagnosis of Autistic Disorder
* Aberrant Behavior Checklist (ABC) Lethargy Subscale Score of 13 or greater

Exclusion Criteria:

* Children with Severe to Profound Mental Retardation
* Weight at Screening Visit \<11 kilograms
* Clinical Global Impressions-Severity Score of 7
* Presence of a Neurodevelopmental Disorder with Possible Associations to Autism: Subjects with Fragile X Syndrome, Tuberous Sclerosis, or other neurodevelopmental disorders known to be associated with autism or autistic features will be excluded.
* Presence of a Psychiatric Disorder that would Require a Specific Type of Treatment: Subjects with major depressive disorder, bipolar disorder, or a psychotic disorder will be excluded because treatment for these disorders often requires specific psychotropic agents. Subjects with an active substance use disorder will be excluded because of safety concerns and problems this would cause in assessing efficacy.
* Presence of a Medical Condition that would make Treatment with D-Cycloserine Less Safe: Subjects with significant cardiac, hepatic, or renal disease will be excluded due to concerns about pharmacokinetic alterations or adverse effects. Subjects with epilepsy or a history of seizures will be excluded due to rare reports of seizures with high doses of D-cycloserine. D-cycloserine is an U.S. FDA Pregnancy Category C drug. Because of the unknown effects of D-cycloserine on the developing human fetus, females of childbearing potential will be given a urine pregnancy test and required to use a suitable form of birth control during the study.
B: Inclusion Criteria:

1. Signed Written Informed Consent

   1. Participants or their legal representative must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal participant care. Participants who do not have the capacity to consent will give developmentally appropriate assent.
   2. Participants must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing.
   3. The subject's parent/caregiver/LAR must be able to speak and understand the local language where the study is conducted sufficiently to understand the nature of the study and to allow for the completion of all study assessments. The same parent/caregiver/LAR must be capable of providing reliable information about the subject's condition, agree to oversee the administration of study drug, and accompany the subject to all clinic visits.
   4. Patient must be able to speak and understand the local language where the study is conducted sufficiently to understand the nature of the study and to allow for the completion of all study assessments.
2. Type of Participant and Target Disease Characteristics

   1. Diagnosis of an Autism Spectrum Disorder according to the DSM-5 criteria
   2. Complex language as defined in ADOS-2 to qualify for a Module 3 or 4.
   3. Current pharmacological treatment regimen affecting behaviour has been stable for at least 6 weeks prior to screening and is expected to be stable during the duration of the study
   4. Current psychotherapeutic/psychosocial interventions affecting behaviour stable for 3 months prior to screening and expected to be stable during the duration of the study (standard regular school breaks and/or annual teacher/classroom change do not qualify for intervention change).
   5. Subjects with a history of seizure disorder must currently be receiving stable treatment with anticonvulsant medication and must have been seizure free for 6 months prior to screening, or must be seizure free for 3 years prior to screening if not currently on a stable (\>3 months) dose of antiepileptics.
3. Age, Residential and Reproductive Status

   1. Male or female participants 5 to 17 years of age at the time of providing consent, inclusive.
   2. Reside with the parent/carer who is interviewed for the Vineland.
   3. Negative pregnancy test for females of childbearing potential (subject has experienced onset of menses) within 24h prior to study treatment starts.
   4. Females of childbearing potential who are sexually active must agree to use a highly effective form of contraception (i.e., existing surgical sterilization, complete abstinence, or a combination of two effective forms of contraception, such as, for example, condoms plus hormonal treatment).
   5. Male participants with female partners of childbearing potential are eligible to participate if they agree to the following conditions:

      * Inform any and all partner(s) of their participation in a clinical drug study and the need to comply with contraception instructions as directed by the investigator.
      * Male participants are required to use a condom for study duration and until end of relevant systemic exposure defined as 7 months after the end of study treatment.
      * Female partners of males participating in the study to consider use of effective methods of contraception until the end of relevant systemic exposure, defined as 7 months after the end of treatment in the male participant.
      * Male participants with a pregnant or breastfeeding partner must agree to remain abstinent from penile vaginal intercourse or use a male condom during each episode of penile penetration during the treatment and until 7 months after the end of study treatment.
      * Refrain from donating sperm for the duration of the study treatment and until 7 months after the end of study treatment.

Exclusion Criteria:

1. Medical Conditions

   a. Subjects with any condition that might interfere with the conduct of the study, confound interpretation of the study results, or endanger their own well-being. This includes, but is not limited to impairment of renal function, evidence or history of malignancy or any significant haematological, endocrine, respiratory, hepatic, cardiovascular or gastrointestinal disease, including any clinically significant abnormalities on ECG. In general, any co-morbid conditions that may interact with study procedures.
2. Prior/Concomitant Therapy

   1. Subjects who are currently receiving treatment with racemic baclofen, vigabatrin, tiagabine, or riluzole or other GABA-related medications (e.g. gabapentin or pregabalin). Only occasional benzodiazepine (or derivative drugs) use (PM, i.e. at night) will be allowed.
   2. Subjects who are currently receiving pharmacologic treatment affecting behaviour (see concomitant medication section) need to have a stable dose during the 6 weeks prior to the screening visit and for the duration of the study.
   3. Participating in programs including non-pharmacologic educational, behavioural, and/or dietary interventions affecting behaviour, participation in these programs must have been continuous during the 3 months prior to screening and participants or their parent/caregiver/LAR may not electively initiate new or modify ongoing interventions for the duration of the study. Typical school vacations are not considered modifications of stable programming.
   4. Subjects who have taken another investigational drug within the last 30 days.
3. Physical and Laboratory Test Findings

   a. Patients with evidence of any significant hematological, endocrine, cardiovascular (including uncorrected symptomatic congenital heart disease), respiratory, renal, hepatic, or gastrointestinal disease, not including mild common pediatric diseases in these areas that are stable (e.g. mild asthma, constipation, etc.), as judged by the investigator.
4. Study Medication Related

   1. Subjects who are not able to take oral medications.
   2. Subjects who have a history of hypersensitivity to racemic baclofen.
   3. Subjects with rare hereditary problems of galactose intolerance, the lactase deficiency or glucose-galactose malabsorption should not take this medicine.
   4. Active peptic ulceration as Baclofen stimulates gastric acid secretion.
   5. Porphyria.
5. Other Exclusion Criteria

   1. Subjects who are currently engaged in illicit drug use or alcohol abuse, according to DSM-5 criteria.
   2. Subjects who have previously participated in a clinical trial of Arbaclofen.
   3. Women who are breastfeeding.
C: Inclusion Criteria:

* Male \& female subjects ages 8-18 years (inclusive).
* Diagnostic Statistical Manual (DSM)-5 Autism Spectrum Disorder (ASD) diagnostic criteria 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 Global Impression-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 glutamate levels): Lamotrigine, Amantadine, N-acetylcysteine, D-cycloserine
* Subjects treated with a psychotropic medication not listed above on a dose that has not been stable for at least 4 weeks prior to study baseline.
* 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
* 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 resolved etiology.
* 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 recent history of substance abuse, there will be a two-week washout period before initiating the trial as an added precaution. There are no known safety issues relating 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 tubular acidosis, 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 the clinician.
* Investigator and his/her immediate family defined as the investigator's spouse, parent, child, grandparent, or grandchild.
D: Inclusion Criteria

1. Male or female outpatients, 10-17 years of age inclusive.
2. Meet Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Diagnostic and Statistical Manual (DSM-IV) criteria will be established by a clinician with expertise with individuals with ASD. Best estimate Diagnosis will be reached using DSM-IV criteria, the Autism Diagnostic Observation Schedule (ADOS-2) and the Autism Diagnostic Interview (ADI-R).
3. Have a Clinician's Global Impression-Severity (CGI-S) score ≥ 4 (moderately ill) at Screening.
4. Verbal and performance scale Intelligence Quotient (IQ) ≥ 70 (both subtests of the Wechsler Abbreviated Scale of Intelligence (WASI-I or WASI-II ≥ 70).
5. If already receiving stable concomitant medications affecting behavior, have continuous participation for 1 month prior to Screening (with the exception of fluoxetine, where a period of 6 weeks is needed), and not electively initiate new or modify ongoing medications for the duration of the study.
6. If already receiving stable non-pharmacologic educational, behavioral, and/or dietary interventions, have continuous participation during the preceding 3 months prior to Screening, and not electively initiate new or modify ongoing interventions for the duration of the study.
7. Have normal physical examination and laboratory test results at Screening. If abnormal, the finding(s) must be deemed not clinically significant by the Treating Clinician.
8. Ability to speak and understand English sufficiently to allow for the completion of all study assessments.
9. Ability to obtain written informed consent from the participant, if developmentally appropriate. If a participant does not have the capacity to consent, ability to obtain assent (if developmentally appropriate), as well as written informed consent from their parent(s)/legal guardian.

Exclusion Criteria

1. Patients born prior to 35 weeks gestational age.
2. Patients with a primary psychiatric diagnosis other than ASD.
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 brain MRI/structural lesion.
4. Pregnant female patients, sexually active female patients on hormonal birth control and sexually active females who do not use at least two types of non-hormonal birth control.
5. 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 with one or more of the following: HIV, Hepatitis B virus, Hepatitis C virus, hemophilia (bleeding problems, recent nose and brain injuries), abnormal blood pressure (hypotension or hypertension), drug abuse, immunity disorder or severe depression.
7. Patients who are currently taking oxytocin or have taken intranasal oxytocin in the past with no response.
8. Patients with a sensitivity to oxytocin or any components of its formulation.
9. Patients unable to tolerate venipuncture procedures for blood sampling.
10. Patients in foster care for whom the province/state is defined as a legal guardian

Answer: B