Nuedexta for the Treatment of Adults With Autism

Study Overview
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Brief Summary
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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
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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.

Official Title
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Nuedexta for Neurobehavioral Symptoms of Adults With Autism Spectrum Disorder

Conditions
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Autism

Intervention / Treatment
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* Drug: Nuedexta
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nuedexta<br>Nuedexta (Dextromethorphan hydrobromide 20 mg/quinidine sulfate 10 mg), oral, once daily | Drug: Nuedexta<br>* Nuedexta (Dextromethorphan hydrobromide 20 mg and quinidine sulfate 10 mg) will be given once daily for 7 days. If well-tolerated, it will be given every 12 hours for the next 7 weeks.<br>* Other names: Dextromethorphan hydrobromide and quinidine sulfate;|
| Placebo Comparator: Placebo<br>Oral, once daily | Other: Placebo<br>* Placebo will be given once daily for 7 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Maladaptive Behaviors | 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. | Baseline and 8 weeks | 
| Primary Safety Endpoints | Number of serious adverse events | Week 0 through week 25 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Aggressive Behavior | 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. | Baseline and 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adults