Autism
Conditions
Keywords
autism, memantine, pediatric, Forest Laboratories, Autism in pediatric patients
Brief summary
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.
Detailed description
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
Interventions
DRUGMemantine - Extended Release (ER)
Memantine - 3mg and 6mg capsules, dose ranging 3 - 18 mg/day in 4 weight groups, administered orally.
DRUGPlacebo
Placebo capsules, once daily, oral administration.
Sponsors
Merz Pharmaceuticals GmbH
Forest Laboratories
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Males or females ages 6 to 12 years * Diagnosis of autistic disorder, according to DSM-IV-TR using Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule (modules 2 & 3). * A knowledgeable caregiver capable of providing reliable information about the patient's condition, able to attend all clinic visits with the patient * Patients over age 12, only if they completed Study MEM-PK-21
Exclusion criteria
* Medical history of active epilepsy/seizure disorder except simple febrile seizures * Participation in any other clinical investigation using an experimental drug within 30 days of the start of this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Extent of Absorption of Memantine (Part One) | Baseline to 144 hours. Measurements were taken 0 (predose), 4, 8, 24, 30, 48, 96 and 144 hours post-dose | Area under the plasma concentration vs. time curve (AUC) for memantine, as measured in units of nanogram x hours per milliliter. |
| Change in Total Raw Score of Social Responsiveness Scale | From Baseline to Week 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Core Autism Treatment Scale-Improvement: Communication | At Week 12 | 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). |
| Change in Children's Communication Checklist-2 (CCC-2) - Speech Subscale | From Baseline to Week 12 | 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). |
| Change in Children's Communication Checklist-2 (CCC-2) - Syntax Subscale | From Baseline to Week 12 | 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). |
| Change in Children's Communication Checklist-2 (CCC-2) - Semantics Subscale | From Baseline to Week 12 | 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). |
| Change in Children's Communication Checklist-2 (CCC-2) - Coherence Subscale | From Baseline to Week 12 | 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). |
| Core Autism Treatment Scale-Improvement: Total Score | At Week 12 | 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). |
| Change in Children's Communication Checklist-2 (CCC-2) - Scripted Language Subscale | From Baseline to Week 12 | 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). |
| Change in Children's Communication Checklist-2 (CCC-2) - Context Subscale | From Baseline to Week 12 | 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). |
| Change in Children's Communication Checklist-2 (CCC-2) - Nonverbal Communication Subscale | From Baseline to Week 12 | 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). |
| Change in Children's Communication Checklist-2 (CCC-2) - Social Relations Subscale | From Baseline to Week 12 | 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). |
| Change in Children's Communication Checklist-2 (CCC-2) - Interests Subscale | From Baseline to Week 12 | 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). |
| Change in Children's Communication Checklist-2 (CCC-2) - Initiation Subscale | From Baseline to Week 12 | 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). |
| Core Autism Treatment Scale-Improvement: Social Interaction | At Week 12 | 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). |
Countries
United States
Participant flow
Recruitment details
Patients for Part One of the study were recruited during a 15 month period from April of 2009, to June of 2010. Patients for Part Two of the study were recruited for a 37 month period from April of 2009 to April of 2012. All study sites were located in the United States.
Pre-assignment details
Part One of the study enrolled 4 patients to determine a safe dosing regimen for Part Two. One patient from Part One of the study also enrolled in Part Two. The 121 patients enrolled in Part Two were randomized after two weeks of single-blind placebo treatment.
Participants by arm
| Arm | Count |
|---|---|
| Part One - Memantine Patients received a single dose of 3-mg memantine extended release capsule, oral administration. | 3 |
| Part Two - Placebo Once daily oral administration of placebo for 12 weeks. | 61 |
| Part Two - Memantine Once daily oral administration of memantine extended release for 12 weeks. Memantine - 3mg and 6mg capsules, dose ranging 3 - 18 mg/day in 4 weight groups. | 60 |
| Total | 124 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Part Two - Double Blind | Adverse Event | 4 | 3 |
| Part Two - Double Blind | Lack of Efficacy | 1 | 0 |
| Part Two - Double Blind | Lost to Follow-up | 0 | 2 |
| Part Two - Double Blind | Other reasons | 2 | 0 |
| Part Two - Double Blind | Protocol Violation | 1 | 0 |
| Part Two - Double Blind | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Part Two - Placebo | Part Two - Memantine | Total | Part One - Memantine |
|---|---|---|---|---|
| Age, Continuous 6 years to 18 years | 8.9 years STANDARD_DEVIATION 2.2 | 9.0 years STANDARD_DEVIATION 2.2 | 9.0 years STANDARD_DEVIATION 0.1 | 9.0 years STANDARD_DEVIATION 2.6 |
| Age, Customized 13 years to 18 years | 1 participants | 1 participants | 2 participants | 0 participants |
| Age, Customized 6 years to 12 years | 60 participants | 59 participants | 122 participants | 3 participants |
| Region of Enrollment United States | 61 participants | 60 participants | 124 participants | 3 participants |
| Sex: Female, Male Female | 12 Participants | 8 Participants | 22 Participants | 2 Participants |
| Sex: Female, Male Male | 49 Participants | 52 Participants | 102 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 31 / 61 | 37 / 60 | 1 / 4 |
| serious Total, serious adverse events | 0 / 61 | 1 / 60 | 0 / 4 |
Outcome results
Primary
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
Population: All of the the 121 randomized patients in Part Two of the study, received at least 1 dose of study drug. The protocol specified Intent-to-Treat (ITT) Population consisted of 107 patients who had at least 1 postbaseline assessment of SRS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Memantine | Change in Total Raw Score of Social Responsiveness Scale | -9.5 units on a scale | Standard Error 2.6 |
| Memantine | Change in Total Raw Score of Social Responsiveness Scale | -9.6 units on a scale | Standard Error 2.5 |
p-value: 0.978195% CI: [-7.2, 7]mixed-model for repeated measures
Primary
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
Population: Four patients enrolled in Part One, receiving a single dose of memantine and having evaluable pharmacokinetic parameters (Pharmacokinetic Population)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Memantine | Extent of Absorption of Memantine (Part One) | 682.53 ng•h/mL | Standard Deviation 217.77 |
Secondary
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
Population: All of the the 121 randomized patients in Part Two of the study, received at least 1 dose of study drug. The protocol specified Intent-to-Treat (ITT) Population consisted of 107 patients who had at least 1 postbaseline assessment of SRS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Memantine | Change in Children's Communication Checklist-2 (CCC-2) - Coherence Subscale | -1.2 units on a scale | Standard Error 0.5 |
| Memantine | Change in Children's Communication Checklist-2 (CCC-2) - Coherence Subscale | -1.2 units on a scale | Standard Error 0.5 |
p-value: 0.959895% CI: [-1.3, 1.3]mixed-model for repeated measures
Secondary
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
Population: All of the the 121 randomized patients in Part Two of the study, received at least 1 dose of study drug. The protocol specified Intent-to-Treat (ITT) Population consisted of 107 patients who had at least 1 postbaseline assessment of SRS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Memantine | Change in Children's Communication Checklist-2 (CCC-2) - Context Subscale | -1.5 units on a scale | Standard Error 0.4 |
| Memantine | Change in Children's Communication Checklist-2 (CCC-2) - Context Subscale | -0.2 units on a scale | Standard Error 0.4 |
p-value: 0.020195% CI: [0.2, 2.5]mixed-model for repeated measures
Secondary
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
Population: All of the the 121 randomized patients in Part Two of the study, received at least 1 dose of study drug. The protocol specified Intent-to-Treat (ITT) Population consisted of 107 patients who had at least 1 postbaseline assessment of SRS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Memantine | Change in Children's Communication Checklist-2 (CCC-2) - Initiation Subscale | -0.8 units on a scale | Standard Error 0.5 |
| Memantine | Change in Children's Communication Checklist-2 (CCC-2) - Initiation Subscale | -0.9 units on a scale | Standard Error 0.4 |
p-value: 0.989895% CI: [-1.3, 1.3]mixed-model for repeated measures
Secondary
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
Population: All of the the 121 randomized patients in Part Two of the study, received at least 1 dose of study drug. The protocol specified Intent-to-Treat (ITT) Population consisted of 107 patients who had at least 1 postbaseline assessment of SRS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Memantine | Change in Children's Communication Checklist-2 (CCC-2) - Interests Subscale | -0.5 units on a scale | Standard Error 0.4 |
| Memantine | Change in Children's Communication Checklist-2 (CCC-2) - Interests Subscale | -0.5 units on a scale | Standard Error 0.4 |
p-value: 0.9595% CI: [-1.2, 1.1]mixed-model for repeated measures
Secondary
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
Population: All of the the 121 randomized patients in Part Two of the study, received at least 1 dose of study drug. The protocol specified Intent-to-Treat (ITT) Population consisted of 107 patients who had at least 1 postbaseline assessment of SRS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Memantine | Change in Children's Communication Checklist-2 (CCC-2) - Nonverbal Communication Subscale | -0.7 units on a scale | Standard Error 0.4 |
| Memantine | Change in Children's Communication Checklist-2 (CCC-2) - Nonverbal Communication Subscale | -0.9 units on a scale | Standard Error 0.4 |
p-value: 0.688995% CI: [-1.3, 0.9]mixed-model for repeated measures
Secondary
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
Population: All of the the 121 randomized patients in Part Two of the study, received at least 1 dose of study drug. The protocol specified Intent-to-Treat (ITT) Population consisted of 107 patients who had at least 1 postbaseline assessment of SRS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Memantine | Change in Children's Communication Checklist-2 (CCC-2) - Scripted Language Subscale | -1.0 units on a scale | Standard Error 0.4 |
| Memantine | Change in Children's Communication Checklist-2 (CCC-2) - Scripted Language Subscale | -0.5 units on a scale | Standard Error 0.4 |
p-value: 0.422895% CI: [-0.7, 1.6]mixed-model for repeated measures
Secondary
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
Population: All of the the 121 randomized patients in Part Two of the study, received at least 1 dose of study drug. The protocol specified Intent-to-Treat (ITT) Population consisted of 107 patients who had at least 1 postbaseline assessment of SRS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Memantine | Change in Children's Communication Checklist-2 (CCC-2) - Semantics Subscale | -0.2 units on a scale | Standard Error 0.3 |
| Memantine | Change in Children's Communication Checklist-2 (CCC-2) - Semantics Subscale | -0.5 units on a scale | Standard Error 0.3 |
p-value: 0.467995% CI: [-1.2, 0.6]mixed-model for repeated measures
Secondary
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
Population: All of the the 121 randomized patients in Part Two of the study, received at least 1 dose of study drug. The protocol specified Intent-to-Treat (ITT) Population consisted of 107 patients who had at least 1 postbaseline assessment of SRS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Memantine | Change in Children's Communication Checklist-2 (CCC-2) - Social Relations Subscale | -1.0 units on a scale | Standard Error 0.4 |
| Memantine | Change in Children's Communication Checklist-2 (CCC-2) - Social Relations Subscale | -0.8 units on a scale | Standard Error 0.4 |
p-value: 0.748195% CI: [-0.9, 1.2]mixed-model for repeated measures
Secondary
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
Population: All of the the 121 randomized patients in Part Two of the study, received at least 1 dose of study drug. The protocol specified Intent-to-Treat (ITT) Population consisted of 107 patients who had at least 1 postbaseline assessment of SRS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Memantine | Change in Children's Communication Checklist-2 (CCC-2) - Speech Subscale | -0.4 units on a scale | Standard Error 0.5 |
| Memantine | Change in Children's Communication Checklist-2 (CCC-2) - Speech Subscale | -0.7 units on a scale | Standard Error 0.5 |
p-value: 0.795% CI: [-1.5, 1]mixed-model for repeated measures
Secondary
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
Population: All of the the 121 randomized patients in Part Two of the study, received at least 1 dose of study drug. The protocol specified Intent-to-Treat (ITT) Population consisted of 107 patients who had at least 1 postbaseline assessment of SRS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Memantine | Change in Children's Communication Checklist-2 (CCC-2) - Syntax Subscale | -1.1 units on a scale | Standard Error 0.4 |
| Memantine | Change in Children's Communication Checklist-2 (CCC-2) - Syntax Subscale | -1.2 units on a scale | Standard Error 0.4 |
p-value: 0.906995% CI: [-1.3, 1.1]mixed-model for repeated measures
Secondary
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
Population: All of the the 121 randomized patients in Part Two of the study, received at least 1 dose of study drug. The protocol specified Intent-to-Treat (ITT) Population consisted of 107 patients who had at least 1 postbaseline assessment of SRS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Memantine | Core Autism Treatment Scale-Improvement: Communication | 18.0 units on a scale | Standard Error 0.4 |
| Memantine | Core Autism Treatment Scale-Improvement: Communication | 17.2 units on a scale | Standard Error 0.4 |
p-value: 0.134495% CI: [-1.9, 0.3]mixed-model for repeated measures
Secondary
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).
Time frame: At Week 12
Population: All of the the 121 randomized patients in Part Two of the study, received at least 1 dose of study drug. The protocol specified Intent-to-Treat (ITT) Population consisted of 107 patients who had at least 1 postbaseline assessment of SRS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Memantine | Core Autism Treatment Scale-Improvement: Social Interaction | 32.4 units on a scale | Standard Error 0.7 |
| Memantine | Core Autism Treatment Scale-Improvement: Social Interaction | 31.1 units on a scale | Standard Error 0.6 |
p-value: 0.145995% CI: [-3.2, 0.5]mixed-model for repeated measures
Secondary
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
Population: All of the the 121 randomized patients in Part Two of the study, received at least 1 dose of study drug. The protocol specified Intent-to-Treat (ITT) Population consisted of 107 patients who had at least 1 postbaseline assessment of SRS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Memantine | Core Autism Treatment Scale-Improvement: Total Score | 50.4 units on a scale | Standard Error 1 |
| Memantine | Core Autism Treatment Scale-Improvement: Total Score | 48.3 units on a scale | Standard Error 1 |
p-value: 0.119795% CI: [-4.9, 0.6]mixed-model for repeated measures