Nuedexta for the Treatment of Adults With Autism

Phase 2

Completed

Brief Summary: Primary: Demonstrate reduced frequency and intensity of maladaptive behaviors as measured by the Aberrant Behavior Checklist (ABC) Irritability subscale in subjects given Nuedexta 8 weeks over subjects given placebo.

Secondary: Demonstrate a trend towards reduced aggressive behavior as measured by Overt Aggression Scale (OAS).

Detailed Description: This is a randomized placebo-controlled crossover study. The parents, neuropsychologists, clinical research coordinator (CRC) and PI will be blinded as to whether subjects are on placebo or Nuedexta.

Nuedexta will be given once daily for 7 days. If well-tolerated, it will be given every 12 hours for the next 7 weeks. Patients may also remain on the once-daily dose if desired.

The study will last 44 weeks. This includes 20 weeks for study enrollment, 8 weeks of treatment/placebo, 4 weeks for washout, and a second 8 week-period of treatment/placebo followed by 4 weeks of washout.

Subjects will be randomized to 8 weeks of Nuedexta/placebo. After the 8 week follow-up visit, there will be a 4 week washout period. At week 12 (second baseline), the groups will crossover for another 8 weeks of Nuedexta/placebo. Study endpoints will be measured in the both groups at weeks 8, 12, and 20. A final study visit will occur at week 24.

Recruitment & Eligibility

Inclusion Criteria

18 to 60 years of age
Have a collateral informant who can attend visit and answer questionnaires pertaining to participant behavior
Diagnosis of autistic spectrum disorder based on the Diagnostic and Statistical Manual, 4th edition, Text Revised (DSM-IV-TR) criteria, developmental history, and Autism Diagnostic Observation Schedule (ADOS); or confirmed diagnosis of autism during childhood through similar methods
Capable of giving informed consent, or have a legal guardian capable of giving consent on the subject's behalf; patient able to assent to participate
Mood issues and frontal lobe type perseveration issues
No medication changes within 30 days and no use of new medications during the course of the study except for non-related conditions approved by the investigators

Exclusion Criteria

Clinically uncontrolled epilepsy
Cardiovascular conditions including cardiac or structural malformation heart failure, prolonged QT interval, history of torsades de pointes, or atrioventricular (AV) block
Known genetic disorders, fragile x, or known brain structural abnormalities, cerebral palsy, head injury, or brain tumor
Known allergy to either dextromethorphan or quinidine
Concurrent or recent use of Monoamine oxidase inhibitor (MAOI) antidepressants pt Nuedexta
Concurrent use of lamotrigine or felbamate or other N-Methyl-D-aspartate (NMDA) agonists or antagonists
Thrombocytopenia, hepatitis, bone marrow depression or lupus-like syndrome
Pregnancy - sexually active females of childbearing potential must be on a reliable form of contraception
Other clinically significant abnormality on physical, neurological, laboratory, vital signs, that could compromise the study or be detrimental to the subject

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Oral, once daily
Nuedexta	Nuedexta	Nuedexta (Dextromethorphan hydrobromide 20 mg/quinidine sulfate 10 mg), oral, once daily

Primary Outcome Measures

Name	Time	Method
Change in Maladaptive Behaviors	Baseline and 8 weeks	Demonstrate a change in frequency and intensity of maladaptive behaviors as measured by the Aberrant Behavior Checklist (ABC) Irritability subscale in subjects given Nuedexta 8 weeks over subjects given placebo. This checklist consists of 20 questions relating to behavior and the reported total score is on a scale from 0 to 60. A lower score can be interpreted as less frequent and/or less intense presentation of the undesirable behavior. The below values are the difference in ABC scores from baseline to 8 weeks. A negative difference indicates improved behavior.
Primary Safety Endpoints	Week 0 through week 25	Number of serious adverse events

Secondary Outcome Measures

Name	Time	Method
Change in Aggressive Behavior	Baseline and 8 weeks	Demonstrate a trend towards reduced aggressive behavior as measured by Overt Aggression Scale (OAS). It consists of a scale from 0 - 40, and a lower score can be interpreted as less frequent and/or less intense presentation of the undesirable behavior. Reported is the mean difference in scores from baseline to 8 weeks. A positive score indicates more aggressive behavior and a negative score indicates less aggressive behavior.