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Trial record 16 of 53 for:    Developmental Disabilities | ( Map: Indiana, United States )

Withdrawal Study of Memantine in Pediatric Patients With Autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified Previously Treated With Memantine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01592747
Recruitment Status : Completed
First Posted : May 7, 2012
Results First Posted : April 24, 2019
Last Update Posted : April 24, 2019
Sponsor:
Information provided by (Responsible Party):
Forest Laboratories

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Autistic Disorder
Autism
Asperger's Disorder
Asperger Syndrome
Autism Spectrum Disorders
Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS)
Interventions Drug: Memantine Hydrochloride (HCl)
Drug: Placebo capsules
Enrollment 479
Recruitment Details Patient recruitment occurred over a ten month period, from September of 2012 to June of 2013, at 92 study sites, located in the Untied States and 14 other countries.
Pre-assignment Details Patients who completed at least 12 weeks of exposure to open-label memantine and met the responder criterion at 2 consecutive visits separated by at least 2 weeks during lead-in study MEM-MD-91 were eligible to enroll into this study.
Arm/Group Title Placebo Memantine Reduced Dose Memantine Full-Dose
Hide Arm/Group Description Dose-matched placebo, oral administration, once per day. Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration once per day. Memantine, 3mg, 6mg, 9mg, 12mg or 15mg, depending on weight group and tolerability. Oral administration, once per day.
Period Title: Overall Study
Started 160 [1] 161 [1] 158 [1]
Completed 44 50 50
Not Completed 116 111 108
Reason Not Completed
Loss of Therapeutic Response             107             108             100
Inclusion/Exclusion criteria not met             0             1             1
Adverse Event             1             0             0
Protocol Violation             4             0             4
Lack of Efficacy             0             1             0
Withdrawal by Subject             2             0             2
Lost to Follow-up             1             0             1
Other Reasons             1             1             0
[1]
Based on Randomized Population
Arm/Group Title Placebo Memantine Reduced Dose Memantine Full-Dose Total
Hide Arm/Group Description Dose-matched placebo, oral administration, once per day. Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration once per day. Memantine, 3mg, 6mg, 9mg, 12mg or 15mg depending on weight group and tolerability. Oral administration, once per day. Total of all reporting groups
Overall Number of Baseline Participants 160 160 157 477
Hide Baseline Analysis Population Description
479 patients were screened and randomized. Of these, 477 patients received at least 1 dose of double-blind investigational product (Safety Population). The baseline characteristics presented here are for the Safety population.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 160 participants 160 participants 157 participants 477 participants
8.9  (2.0) 9.2  (1.9) 9.2  (1.9) 9.1  (1.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 160 participants 160 participants 157 participants 477 participants
Female
18
  11.3%
28
  17.5%
25
  15.9%
71
  14.9%
Male
142
  88.8%
132
  82.5%
132
  84.1%
406
  85.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 160 participants 160 participants 157 participants 477 participants
Hispanic or Latino
23
  14.4%
22
  13.8%
15
   9.6%
60
  12.6%
Not Hispanic or Latino
137
  85.6%
138
  86.3%
142
  90.4%
417
  87.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 160 participants 160 participants 157 participants 477 participants
White 138 141 140 419
Black or African American 10 9 7 26
Asian 7 5 8 20
American Indian or Alaska Native 0 1 0 1
Native Hawaiian or Other Pacific Islander 1 1 0 2
Other 4 3 2 9
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 160 participants 160 participants 157 participants 477 participants
United States
134
  83.8%
125
  78.1%
126
  80.3%
385
  80.7%
Belgium
2
   1.3%
1
   0.6%
1
   0.6%
4
   0.8%
Colombia
1
   0.6%
2
   1.3%
2
   1.3%
5
   1.0%
Estonia
0
   0.0%
1
   0.6%
0
   0.0%
1
   0.2%
France
1
   0.6%
4
   2.5%
2
   1.3%
7
   1.5%
Hungary
3
   1.9%
3
   1.9%
2
   1.3%
8
   1.7%
Iceland
0
   0.0%
3
   1.9%
0
   0.0%
3
   0.6%
Italy
2
   1.3%
1
   0.6%
1
   0.6%
4
   0.8%
Korea, Republic of
6
   3.8%
3
   1.9%
5
   3.2%
14
   2.9%
New Zealand
0
   0.0%
1
   0.6%
1
   0.6%
2
   0.4%
Poland
5
   3.1%
6
   3.8%
10
   6.4%
21
   4.4%
Serbia
3
   1.9%
6
   3.8%
5
   3.2%
14
   2.9%
South Africa
0
   0.0%
0
   0.0%
1
   0.6%
1
   0.2%
Spain
1
   0.6%
0
   0.0%
1
   0.6%
2
   0.4%
Ukraine
2
   1.3%
4
   2.5%
0
   0.0%
6
   1.3%
Autism Spectrum Disorder Subtype  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 160 participants 160 participants 157 participants 477 participants
Autism
101
  63.1%
99
  61.9%
100
  63.7%
300
  62.9%
Asperger's Disorder
30
  18.8%
30
  18.8%
27
  17.2%
87
  18.2%
PDD-NOS
29
  18.1%
31
  19.4%
30
  19.1%
90
  18.9%
1.Primary Outcome
Title Proportion of Patients Meeting the Criterion for Loss of Therapeutic Response (LTR) by the End of the Study (Based on Observed Cases)
Hide Description Loss of Therapeutic response is defined as a worsening (increase) of at least 10 points in Social Responsiveness Scale (SRS) total raw score relative to the Visit 1 (randomization) score. The Social Responsiveness Scale (SRS) is a 65-item informant-rated assessment with total raw score 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 Baseline (Visit 1) to week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were based on the Intent-to-treat (ITT) Population. Of the 479 randomized patients, 471 patients were in the ITT Population (ie, had at least 1 dose of double-blind investigational product and at least 1 assessment of the Social Responsiveness Scale (SRS) total raw score during the double-blind treatment period.)
Arm/Group Title Placebo Memantine Reduced Dose Memantine Full-Dose
Hide Arm/Group Description:
Dose-matched placebo, oral administration, once per day.
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration, once per day.
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg; oral administration. Once per day.
Overall Number of Participants Analyzed 158 160 153
Measure Type: Number
Unit of Measure: Percentage of patients with LTR
69.0 67.5 66.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Memantine Full-Dose
Comments Cochran-Mantel-Haenszel test was performed controlling for Autism Spectrum Disorder (ASD) subtype. Odds ratio was calculated for placebo vs. memantine full dose.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6590
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.1
Confidence Interval (2-Sided) 95%
0.7 to 1.8
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Memantine Reduced Dose
Comments Cochran-Mantel-Haenszel test was performed controlling for Autism Spectrum Disorder (ASD) subtype. Odds ratio was calculated for placebo vs. Memantine reduced dose
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7839
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.1
Confidence Interval (2-Sided) 95%
0.7 to 1.7
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Time to First Loss of Therapeutic (LTR) Response
Hide Description Time to the first visit when a patient shows LTR following randomization to memantine or placebo.
Time Frame Baseline to week 12
Hide Outcome Measure Data
Hide Analysis Population Description
All efficacy analyses were based on the Intent-to-treat (ITT) Population. Of the 479 randomized patients, 471 patients were in the ITT Population (ie, had at least 1 dose of double-blind investigational product and at least 1 assessment of the Social Responsiveness Scale (SRS) total raw score during the double-blind treatment period.)
Arm/Group Title Placebo Memantine Reduced Dose Memantine Full-Dose
Hide Arm/Group Description:
Dose-matched placebo, oral administration, once per day.
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration, once per day.
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg depending on weight group and tolerability. Oral administration, once per day.
Overall Number of Participants Analyzed 158 160 153
Median (95% Confidence Interval)
Unit of Measure: Days
29
(28 to 42)
33
(28 to 56)
30
(28 to 44)
3.Secondary Outcome
Title Change From Baseline in Children’s Communication Checklist-2 (CCC-2) - Speech Subscale at Week 12
Hide Description The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties (items 1-50) and strengths (items 51-70) in communication. There are 10 sub-scales consisting of 7 items each. 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).
Time Frame Baseline (Visit 1) to week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Of the 479 randomized patients, 471 patients were included in the Intent to Treat (ITT) Population. Within the ITT population, 466 patients had post-baseline assessment of the Children's Communication Checklist-2 (CCC-2).
Arm/Group Title Placebo Memantine Reduced Dose Memantine Full-Dose
Hide Arm/Group Description:
Dose-matched placebo, oral administration, once per day.
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration, once per day.
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg depending on weight group and tolerability. Oral administration, once per day.
Overall Number of Participants Analyzed 154 159 153
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.1  (0.2) 0.1  (0.2) 0.2  (0.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Memantine Full-Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8136
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.5 to 0.7
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Memantine Reduced Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9244
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.0
Confidence Interval (2-Sided) 95%
-0.6 to 0.5
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Children’s Communication Checklist-2 (CCC-2) - Syntax Subscale at Week 12
Hide Description The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties (items 1-50) and strengths (items 51-70) in communication. There are 10 sub-scales consisting of 7 items each. 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).
Time Frame Baseline (Visit 1) to week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Of the 479 randomized patients, 471 patients were included in the Intent to Treat (ITT) Population. Within the ITT population, 466 patients had post-baseline assessment of the Children's Communication Checklist-2 (CCC-2).
Arm/Group Title Placebo Memantine Reduced Dose Memantine Full-Dose
Hide Arm/Group Description:
Dose-matched placebo, oral administration, once per day.
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration, once per day.
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg depending on weight group and tolerability. Oral administration, once per day.
Overall Number of Participants Analyzed 154 159 153
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.0  (0.2) 0.3  (0.2) 0.1  (0.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Memantine Full-Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7611
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.5 to 0.7
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Memantine Reduced Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3176
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.3 to 0.9
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Children’s Communication Checklist-2 (CCC-2) - Semantics Subscale at Week 12
Hide Description The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties (items 1-50) and strengths (items 51-70) in communication. There are 10 sub-scales consisting of 7 items each. 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).
Time Frame Baseline (Visit 1) to week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Of the 479 randomized patients, 471 patients were included in the Intent to Treat (ITT) Population. Within the ITT population, 466 patients had post-baseline assessment of the Children's Communication Checklist-2 (CCC-2).
Arm/Group Title Placebo Memantine Reduced Dose Memantine Full-Dose
Hide Arm/Group Description:
Dose-matched placebo, oral administration, once per day.
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration, once per day.
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg depending on weight group and tolerability. Oral administration, once per day.
Overall Number of Participants Analyzed 154 159 153
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.3  (0.2) 0.7  (0.2) 0.3  (0.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Memantine Full-Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9020
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.5 to 0.6
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Memantine Reduced Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1279
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.1 to 1.0
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Children’s Communication Checklist-2 (CCC-2) - Coherence Subscale at Week 12
Hide Description The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties (items 1-50) and strengths (items 51-70) in communication. There are 10 sub-scales consisting of 7 items each. 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).
Time Frame Baseline (Visit 1) to week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Of the 479 randomized patients, 471 patients were included in the Intent to Treat (ITT) Population. Within the ITT population, 466 patients had post-baseline assessment of the Children's Communication Checklist-2 (CCC-2).
Arm/Group Title Placebo Memantine Reduced Dose Memantine Full-Dose
Hide Arm/Group Description:
Dose-matched placebo, oral administration, once per day.
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration, once per day.
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg depending on weight group and tolerability. Oral administration, once per day.
Overall Number of Participants Analyzed 154 159 153
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.7  (0.3) 1.0  (0.3) 1.0  (0.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Memantine Full-Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4144
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.4 to 1.1
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Memantine Reduced Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4212
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.4 to 1.0
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in Children’s Communication Checklist-2 (CCC-2) - Initiation Subscale at Week 12
Hide Description The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties (items 1-50) and strengths (items 51-70) in communication. There are 10 sub-scales consisting of 7 items each. 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).
Time Frame Baseline (Visit 1) to week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Of the 479 randomized patients, 471 patients were included in the Intent to Treat (ITT) Population. Within the ITT population, 466 patients had post-baseline assessment of the Children's Communication Checklist-2 (CCC-2).
Arm/Group Title Placebo Memantine Reduced Dose Memantine Full-Dose
Hide Arm/Group Description:
Dose-matched placebo, oral administration, once per day.
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration, once per day.
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg depending on weight group and tolerability. Oral administration, once per day.
Overall Number of Participants Analyzed 154 159 153
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
1.4  (0.3) 1.6  (0.3) 1.2  (0.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Memantine Full-Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6238
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.9 to 0.5
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Memantine Reduced Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5957
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.5 to 0.9
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in Children’s Communication Checklist-2 (CCC-2) - Scripted Language Subscale at Week 12
Hide Description The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties (items 1-50) and strengths (items 51-70) in communication. There are 10 sub-scales consisting of 7 items each. 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).
Time Frame Baseline (Visit 1) to week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Of the 479 randomized patients, 471 patients were included in the Intent to Treat (ITT) Population. Within the ITT population, 466 patients had post-baseline assessment of the Children's Communication Checklist-2 (CCC-2).
Arm/Group Title Placebo Memantine Reduced Dose Memantine Full-Dose
Hide Arm/Group Description:
Dose-matched placebo, oral administration, once per day.
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration, once per day.
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg depending on weight group and tolerability. Oral administration, once per day.
Overall Number of Participants Analyzed 154 159 153
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.8  (0.2) 1.1  (0.2) 0.9  (0.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Memantine Full-Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8640
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.6 to 0.7
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Memantine Reduced Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4362
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.4 to 0.9
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in Children’s Communication Checklist-2 (CCC-2) - Context Subscale at Week 12
Hide Description The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties (items 1-50) and strengths (items 51-70) in communication. There are 10 sub-scales consisting of 7 items each. 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).
Time Frame Baseline (Visit 1) to week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Of the 479 randomized patients, 471 patients were included in the Intent to Treat (ITT) Population. Within the ITT population, 466 patients had post-baseline assessment of the Children's Communication Checklist-2 (CCC-2).
Arm/Group Title Placebo Memantine Reduced Dose Memantine Full-Dose
Hide Arm/Group Description:
Dose-matched placebo, oral administration, once per day.
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration, once per day.
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg depending on weight group and tolerability. Oral administration, once per day.
Overall Number of Participants Analyzed 154 159 153
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.9  (0.3) 0.8  (0.3) 0.8  (0.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Memantine Full-Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7182
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.8 to 0.6
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Memantine Reduced Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8390
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.8 to 0.6
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in Children’s Communication Checklist-2 (CCC-2) - Nonverbal Communication Subscale at Week 12
Hide Description The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties (items 1-50) and strengths (items 51-70) in communication. There are 10 sub-scales consisting of 7 items each. 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).
Time Frame Baseline (Visit 1) to week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Of the 479 randomized patients, 471 patients were included in the Intent to Treat (ITT) Population. Within the ITT population, 466 patients had post-baseline assessment of the Children's Communication Checklist-2 (CCC-2).
Arm/Group Title Placebo Memantine Reduced Dose Memantine Full-Dose
Hide Arm/Group Description:
Dose-matched placebo, oral administration, once per day.
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration, once per day.
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg depending on weight group and tolerability. Oral administration, once per day.
Overall Number of Participants Analyzed 154 159 153
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
1.2  (0.3) 1.5  (0.3) 1.8  (0.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Memantine Full-Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0813
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-0.1 to 1.4
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Memantine Reduced Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4365
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.4 to 1.0
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in Children’s Communication Checklist-2 (CCC-2) - Social Relations Subscale at Week 12
Hide Description The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties (items 1-50) and strengths (items 51-70) in communication. There are 10 sub-scales consisting of 7 items each. 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).
Time Frame Baseline (Visit 1) to week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Of the 479 randomized patients, 471 patients were included in the Intent to Treat (ITT) Population. Within the ITT population, 466 patients had post-baseline assessment of the Children's Communication Checklist-2 (CCC-2).
Arm/Group Title Placebo Memantine Reduced Dose Memantine Full-Dose
Hide Arm/Group Description:
Dose-matched placebo, oral administration, once per day.
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration, once per day.
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg depending on weight group and tolerability. Oral administration, once per day.
Overall Number of Participants Analyzed 154 159 153
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
1.5  (0.3) 1.8  (0.3) 1.8  (0.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Memantine Full-Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4213
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.4 to 1.0
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Memantine Reduced Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4267
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.4 to 1.0
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline in Children’s Communication Checklist-2 (CCC-2) - Interests Subscale at Week 12
Hide Description The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties (items 1-50) and strengths (items 51-70) in communication. There are 10 sub-scales consisting of 7 items each. 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).
Time Frame Baseline (Visit 1) to week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Of the 479 randomized patients, 471 patients were included in the Intent to Treat (ITT) Population. Within the ITT population, 466 patients had post-baseline assessment of the Children's Communication Checklist-2 (CCC-2).
Arm/Group Title Placebo Memantine Reduced Dose Memantine Full-Dose
Hide Arm/Group Description:
Dose-matched placebo, oral administration, once per day.
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration, once per day.
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg depending on weight group and tolerability. Oral administration, once per day.
Overall Number of Participants Analyzed 154 159 153
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.9  (0.3) 1.3  (0.3) 1.2  (0.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Memantine Full-Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3713
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.3
Confidence Interval 95%
-0.4 to 1.0
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Memantine Reduced Dose
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2855
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.3 to 1.1
Estimation Comments [Not Specified]
Time Frame Adverse events were collected for a 14 month period from September of 2012 to October of 2013 at 92 study centers in the United States and 14 other countries.
Adverse Event Reporting Description Safety results are based on Safety Population (ie, all randomized patients who took at least 1 dose of double-blind study drug).
 
Arm/Group Title Placebo Memantine Reduced Dose Memantine Full-Dose
Hide Arm/Group Description Dose-matched placebo, oral administration, once per day. Memantine, 3mg every other day, 3mg per day, or 6mg per day. Oral administration. Memantine, 3mg, 6mg, 9mg, 12mg or 15mg; oral administration. Once per day.
All-Cause Mortality
Placebo Memantine Reduced Dose Memantine Full-Dose
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Memantine Reduced Dose Memantine Full-Dose
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/160 (0.00%)   1/160 (0.63%)   0/157 (0.00%) 
Infections and infestations       
Furuncle  1  0/160 (0.00%)  1/160 (0.63%)  0/157 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Memantine Reduced Dose Memantine Full-Dose
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/160 (5.00%)   5/160 (3.13%)   4/157 (2.55%) 
General disorders       
Irritability  1  8/160 (5.00%)  5/160 (3.13%)  4/157 (2.55%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
All data generated in this study are the property of Forest Research Institute, Inc. An integrated clinical and statistical report will be prepared at the completion of the study. Publication of the results by the Investigator will be subject to mutual agreement between the Investigator and Forest Research Institute, Inc.
Results Point of Contact
Name/Title: Therapeutic Area Head
Organization: Allergan
Phone: 714-246-4500
Responsible Party: Forest Laboratories
ClinicalTrials.gov Identifier: NCT01592747     History of Changes
Other Study ID Numbers: MEM-MD-68
First Submitted: May 3, 2012
First Posted: May 7, 2012
Results First Submitted: September 11, 2014
Results First Posted: April 24, 2019
Last Update Posted: April 24, 2019