The purpose of this study is to investigate the safety and efficacy of memantine extended release, as well as its extent of absorption in pediatric patients with autism.
This is a multicenter, two-part study in pediatric (ages 6 to 18 years) patients diagnosed with autism. Patients participating in Part One will receive a single open-label dose of memantine. Blood samples for pharmacokinetic analysis will be collected. Part Two is a randomized, double-blind, placebo-controlled 12-week efficacy and safety study evaluating change in all core domains (social interactions, communication, and restricted interests and repetitive behaviors) of autism. In the Forest autism trials conducted in children ages 6-12, dosing with an extended release formulation of memantine was weight-based. These weight based dose limits were selected to ensure exposure in terms of area under the curve (AUC) was less than the predefined limit of 2100 ng∙h/mL that represented a 10-fold lower exposure than observed at the NOAEL (No observed adverse effect level) of 15 mg/kg/day in juvenile rats. The weight-based dose limits in these studies were as follows: * Group A: ≥ 60 kg; max 15 mg/day * Group B: 40-59 kg; max 9 mg/day * Group C: 20-39 kg; max 6 mg/day * Group D: \< 20 kg; max 3 mg/day
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
124
Memantine - 3mg and 6mg capsules, dose ranging 3 - 18 mg/day in 4 weight groups, administered orally.
Placebo capsules, once daily, oral administration.
Forest Investigative Site
Phoenix, Arizona, United States
Forest Investigative Site
Sacramento, California, United States
Extent of Absorption of Memantine (Part One)
Area under the plasma concentration vs. time curve (AUC) for memantine, as measured in units of nanogram x hours per milliliter.
Time frame: Baseline to 144 hours. Measurements were taken 0 (predose), 4, 8, 24, 30, 48, 96 and 144 hours post-dose
Change in Total Raw Score of Social Responsiveness Scale
The Social Responsiveness Scale (SRS) is a 65-item informant-rated assessment, ranging from 0 (no impairment) to 195 (severe social impairment). Each item is associated with 1 of 5 subscales (social awareness, social cognition, social communication, social motivation and autistic mannerisms). Each item is rated on a 4-point scale from 1 (not true) to 4 (almost always true). The scores are then transposed to a scale from 0 to 3 and scores are summed within each of the 5 subscales. A higher score indicates greater severity of social impairment.
Time frame: From Baseline to Week 12
Core Autism Treatment Scale-Improvement: Total Score
The Core Autism Treatment Scale-Improvement (CATS-I) is based on rating 14 items from 1 (very much improved) to 7 (very much worse) with a total score ranging from 14 (improved) to 98 (worsened). The Core Autism Treatment Scale-Improvement (CATS-I) is designed to utilize a comparison between pretreatment ratings of Core Autism Treatment Scale-Severity (CATS-S) and ratings of improvement after start of therapy (CATS-I). Both parts of the CATS contain 14 items testing for social interaction (items 1-9) and communication (items 10-14). Each of these items is rated from 1 (indicating most benign) to 7 (indicating most severe).
Time frame: At Week 12
Core Autism Treatment Scale-Improvement: Social Interaction
The Core Autism Treatment Scale-Improvement (CATS-I) Social Interaction Subscale is based on rating 9 items from 1 (very much improved) to 7 (very much worse) with a total score ranging from 9 (improved) to 63 (worsened). The Core Autism Treatment Scale-Improvement (CATS-I) is designed to utilize a comparison between pretreatment ratings of Core Autism Treatment Scale-Severity (CATS-S) and ratings of improvement after start of therapy (CATS-I). Both parts of the CATS contain 14 items testing for social interaction (items 1-9) and communication (items 10-14). Each of these items is rated from 1 (indicating most benign) to 7 (indicating most severe).
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Forest Investigative Site
San Francisco, California, United States
Forest Investigative Site
Santa Ana, California, United States
Forest Investigative Site
Stanford, California, United States
Forest Investigative Site
Jacksonville Beach, Florida, United States
Forest Investigative Site
St. Petersburg, Florida, United States
Forest Investigative Site
Hoffman Estates, Illinois, United States
Forest Investigative site
Naperville, Illinois, United States
Forest Investigative Site
Indianapolis, Indiana, United States
...and 7 more locations
Time frame: At Week 12
Core Autism Treatment Scale-Improvement: Communication
The Core Autism Treatment Scale-Improvement (CATS-I) Communication Subscale is based on rating 5 items from 1 (very much improved) to 7 (very much worse) with a total score ranging from 5 (improved) to 35 (worsened). The Core Autism Treatment Scale-Improvement (CATS-I) is designed to utilize a comparison between pretreatment ratings of Core Autism Treatment Scale-Severity (CATS-S) and ratings of improvement after start of therapy (CATS-I). Both parts of the CATS contain 14 items testing for social interaction (items 1-9) and communication (items 10-14). Each of these items is rated from 1 (indicating most benign) to 7 (indicating most severe).
Time frame: At Week 12
Change in Children's Communication Checklist-2 (CCC-2) - Speech Subscale
The Children's Communication Checklist-2 (CCC-2) Speech Subscale consists of 7 items rated from 0 (less than once a week or never) to 3 (several times \[more than twice\] a day or always), with a total raw score of 0 (mildest) to 21 (most severe). The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties children may have (across 10 different subscales, consisting of 7 items each) that affect communication (items 1-50), as well as strengths that children may demonstrate when communicating with others (items 51-70).
Time frame: From Baseline to Week 12
Change in Children's Communication Checklist-2 (CCC-2) - Syntax Subscale
The Children's Communication Checklist-2 (CCC-2) Syntax Subscale consists of 7 items rated from 0 (less than once a week or never) to 3 (several times \[more than twice\] a day or always), with a total raw score of 0 (mildest) to 21 (most severe). The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties children may have (across 10 different subscales, consisting of 7 items each) that affect communication (items 1-50), as well as strengths that children may demonstrate when communicating with others (items 51-70).
Time frame: From Baseline to Week 12
Change in Children's Communication Checklist-2 (CCC-2) - Semantics Subscale
The Children's Communication Checklist-2 (CCC-2) Semantics Subscale consists of 7 items rated from 0 (less than once a week or never) to 3 (several times \[more than twice\] a day or always), with a total raw score of 0 (mildest) to 21 (most severe). The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties children may have (across 10 different subscales, consisting of 7 items each) that affect communication (items 1-50), as well as strengths that children may demonstrate when communicating with others (items 51-70).
Time frame: From Baseline to Week 12
Change in Children's Communication Checklist-2 (CCC-2) - Coherence Subscale
The Children's Communication Checklist-2 (CCC-2) Coherence Subscale consists of 7 items rated from 0 (less than once a week or never) to 3 (several times \[more than twice\] a day or always), with a total raw score of 0 (mildest) to 21 (most severe). The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties children may have (across 10 different subscales, consisting of 7 items each) that affect communication (items 1-50), as well as strengths that children may demonstrate when communicating with others (items 51-70).
Time frame: From Baseline to Week 12
Change in Children's Communication Checklist-2 (CCC-2) - Initiation Subscale
The Children's Communication Checklist-2 (CCC-2) Initiation Subscale consists of 7 items rated from 0 (less than once a week or never) to 3 (several times \[more than twice\] a day or always), with a total raw score of 0 (mildest) to 21 (most severe). The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties children may have (across 10 different subscales, consisting of 7 items each) that affect communication (items 1-50), as well as strengths that children may demonstrate when communicating with others (items 51-70).
Time frame: From Baseline to Week 12
Change in Children's Communication Checklist-2 (CCC-2) - Scripted Language Subscale
The Children's Communication Checklist-2 (CCC-2) Scripted Language Subscale consists of 7 items rated from 0 (less than once a week or never) to 3 (several times \[more than twice\] a day or always), with a total raw score of 0 (mildest) to 21 (most severe). The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties children may have (across 10 different subscales, consisting of 7 items each) that affect communication (items 1-50), as well as strengths that children may demonstrate when communicating with others (items 51-70).
Time frame: From Baseline to Week 12
Change in Children's Communication Checklist-2 (CCC-2) - Context Subscale
The Children's Communication Checklist-2 (CCC-2) Context Subscale consists of 7 items rated from 0 (less than once a week or never) to 3 (several times \[more than twice\] a day or always), with a total raw score of 0 (mildest) to 21 (most severe). The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties children may have (across 10 different subscales, consisting of 7 items each) that affect communication (items 1-50), as well as strengths that children may demonstrate when communicating with others (items 51-70).
Time frame: From Baseline to Week 12
Change in Children's Communication Checklist-2 (CCC-2) - Nonverbal Communication Subscale
The Children's Communication Checklist-2 (CCC-2) Nonverbal Communication Subscale consists of 7 items rated from 0 (less than once a week or never) to 3 (several times \[more than twice\] a day or always), with a total raw score of 0 (mildest) to 21 (most severe). The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties children may have (across 10 different subscales, consisting of 7 items each) that affect communication (items 1-50), as well as strengths that children may demonstrate when communicating with others (items 51-70).
Time frame: From Baseline to Week 12
Change in Children's Communication Checklist-2 (CCC-2) - Social Relations Subscale
The Children's Communication Checklist-2 (CCC-2) Social Relations Subscale consists of 7 items rated from 0 (less than once a week or never) to 3 (several times \[more than twice\] a day or always), with a total raw score of 0 (mildest) to 21 (most severe). The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties children may have (across 10 different subscales, consisting of 7 items each) that affect communication (items 1-50), as well as strengths that children may demonstrate when communicating with others (items 51-70).
Time frame: From Baseline to Week 12
Change in Children's Communication Checklist-2 (CCC-2) - Interests Subscale
The Children's Communication Checklist-2 (CCC-2) Interests Subscale consists of 7 items rated from 0 (less than once a week or never) to 3 (several times \[more than twice\] a day or always), with a total raw score of 0 (mildest) to 21 (most severe). The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties children may have (across 10 different subscales, consisting of 7 items each) that affect communication (items 1-50), as well as strengths that children may demonstrate when communicating with others (items 51-70).
Time frame: From Baseline to Week 12