An Open-Label Safety Study of Memantine in Pediatric Patients With Autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of memantine in pediatric (6-12 years old) patients with autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) and to identify responders for participation in a follow-up randomized withdrawal study.

Detailed Description
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This 50-week multicenter and multinational clinical study is comprised of a 2-week screening period, a 6-week open-label dose-titration period followed by a variable duration maintenance period (up to 42 weeks). Patients with at least 12 weeks of investigational product exposure who meet the protocol specified responder criterion at two consecutive visits separated by at least two weeks are eligible to transition to a randomized withdrawal study. A responder is defined as a patient who demonstrates at least a 10 point improvement (reduction in score) in the Social Responsiveness Scale (SRS) total raw score relative to the Visit 1 total raw score. Weight based dose limits were selected in this study to ensure that exposure in terms of area under the curve (AUC) was less than the predefined limit of 2100 ng·h/mL which represents a 10-fold lower exposure than observed at the No observed adverse effect level (NOAEL) of 15 mg/kg/day in juvenile rats. The weight-based dose limits in this study were as follows: Group A: ≥ 60 kg; maximum 15 mg/day Group B: 40-59 kg; maximum 9 mg/day Group C: 20-39 kg; maximum 6 mg/day Group D: < 20 kg; maximum 3 mg/day

Official Title
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An Open-Label Study of the Safety and Tolerability of Memantine in Pediatric Patients With Autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS)

Conditions
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Autism Spectrum Disorder (ASD), Autism, Autistic Disorder, Asperger's Disorder, Asperger's, Pediatric Autism, Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS)

Intervention / Treatment
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* Drug: Memantine Hydrochloride (HCl)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female outpatients. Age of 6-12. Meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnostic criteria for autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) 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 Exclusion Criteria: Have enrolled in Study MEM-MD-57A Medical conditions that might interfere with the conduct of the study, confound interpretation of the study results, or endanger the patient's well-being. Participation in any other clinical investigation using an experimental drug within 30 days of screening. Having any primary psychiatric (Axis I) diagnosis other than autism, Asperger's Disorder, and PDD-NOS. Meeting DSM-IV-TR criteria for bipolar I disorder, psychotic disorder not otherwise specified, posttraumatic stress disorder, schizophrenia, or major depressive disorder within the past 6 months

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 12 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Memantine Hydrochloride (HCl)<br>Once daily oral administration of open-label memantine for up to 48 weeks: 6-week dose-titration period followed by up to 42-week maintenance period. | Drug: Memantine Hydrochloride (HCl)<br>* Memantine extended release 3-mg capsules; the dosages studied ranged from 3 - 15 mg/day; weight based dosing in 4 weight groups; oral administration. Dosing is once daily for up to 48 weeks.<br>* Other names: Namenda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Confirmed Social Responsiveness Scale (SRS) Responders | A confirmed SRS responder was defined as a patient who had at least 12 weeks of exposure to memantine, and a ≥ 10-point reduction in the SRS total raw score relative to baseline at 2 consecutive visits separated by at least 2 weeks. The SRS is a 65-item, caregiver-rated assessment scale that measures observable items on social behavior and social language use, as well as characteristics of autism in a naturalistic social setting. Each item is rated on a scale from 0 (never true) to 3 (almost always true). The SRS total raw score ranges from 0 to 195; a higher score indicates greater severity of social impairment. | Visit 1 (Baseline) to Visit 8 (week 48/Final Visit) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autism Spectrum Disorder (ASD), Autism, Autistic Disorder, Asperger's Disorder, Asperger's, Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS), Memantine, Pediatric Disorder