Trial Outcomes & Findings for Withdrawal Study of Memantine in Pediatric Patients With Autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified Previously Treated With Memantine (NCT NCT01592747)

NCT ID: NCT01592747

Last Updated: 2019-04-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

479 participants

Primary outcome timeframe

Baseline (Visit 1) to week 12

Results posted on

2019-04-24

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure
Placebo
Dose-matched placebo, oral administration, once per day.
Memantine Reduced Dose
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration once per day.
Memantine Full-Dose
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg, depending on weight group and tolerability. Oral administration, once per day.
Overall Study
STARTED
160
161
158
Overall Study
COMPLETED
44
50
50
Overall Study
NOT COMPLETED
116
111
108

Reasons for withdrawal

Reasons for withdrawal
Measure
Placebo
Dose-matched placebo, oral administration, once per day.
Memantine Reduced Dose
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration once per day.
Memantine Full-Dose
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg, depending on weight group and tolerability. Oral administration, once per day.
Overall Study
Loss of Therapeutic Response
107
108
100
Overall Study
Inclusion/Exclusion criteria not met
0
1
1
Overall Study
Adverse Event
1
0
0
Overall Study
Protocol Violation
4
0
4
Overall Study
Lack of Efficacy
0
1
0
Overall Study
Withdrawal by Subject
2
0
2
Overall Study
Lost to Follow-up
1
0
1
Overall Study
Other Reasons
1
1
0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Placebo
n=160 Participants
Dose-matched placebo, oral administration, once per day.
Memantine Reduced Dose
n=160 Participants
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration once per day.
Memantine Full-Dose
n=157 Participants
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg depending on weight group and tolerability. Oral administration, once per day.
Total
n=477 Participants
Total of all reporting groups
Ethnicity (NIH/OMB)
Hispanic or Latino
23 Participants
n=5 Participants
22 Participants
n=7 Participants
15 Participants
n=5 Participants
60 Participants
n=4 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
137 Participants
n=5 Participants
138 Participants
n=7 Participants
142 Participants
n=5 Participants
417 Participants
n=4 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Race/Ethnicity, Customized
White
138 Participants
n=5 Participants
141 Participants
n=7 Participants
140 Participants
n=5 Participants
419 Participants
n=4 Participants
Race/Ethnicity, Customized
Black or African American
10 Participants
n=5 Participants
9 Participants
n=7 Participants
7 Participants
n=5 Participants
26 Participants
n=4 Participants
Race/Ethnicity, Customized
Asian
7 Participants
n=5 Participants
5 Participants
n=7 Participants
8 Participants
n=5 Participants
20 Participants
n=4 Participants
Age, Continuous
8.9 years
STANDARD_DEVIATION 2.0 • n=5 Participants
9.2 years
STANDARD_DEVIATION 1.9 • n=7 Participants
9.2 years
STANDARD_DEVIATION 1.9 • n=5 Participants
9.1 years
STANDARD_DEVIATION 1.9 • n=4 Participants
Sex: Female, Male
Female
18 Participants
n=5 Participants
28 Participants
n=7 Participants
25 Participants
n=5 Participants
71 Participants
n=4 Participants
Sex: Female, Male
Male
142 Participants
n=5 Participants
132 Participants
n=7 Participants
132 Participants
n=5 Participants
406 Participants
n=4 Participants
Race/Ethnicity, Customized
American Indian or Alaska Native
0 Participants
n=5 Participants
1 Participants
n=7 Participants
0 Participants
n=5 Participants
1 Participants
n=4 Participants
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
1 Participants
n=5 Participants
1 Participants
n=7 Participants
0 Participants
n=5 Participants
2 Participants
n=4 Participants
Race/Ethnicity, Customized
Other
4 Participants
n=5 Participants
3 Participants
n=7 Participants
2 Participants
n=5 Participants
9 Participants
n=4 Participants
Region of Enrollment
United States
134 Participants
n=5 Participants
125 Participants
n=7 Participants
126 Participants
n=5 Participants
385 Participants
n=4 Participants
Region of Enrollment
Belgium
2 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
4 Participants
n=4 Participants
Region of Enrollment
Colombia
1 Participants
n=5 Participants
2 Participants
n=7 Participants
2 Participants
n=5 Participants
5 Participants
n=4 Participants
Region of Enrollment
Estonia
0 Participants
n=5 Participants
1 Participants
n=7 Participants
0 Participants
n=5 Participants
1 Participants
n=4 Participants
Region of Enrollment
France
1 Participants
n=5 Participants
4 Participants
n=7 Participants
2 Participants
n=5 Participants
7 Participants
n=4 Participants
Region of Enrollment
Hungary
3 Participants
n=5 Participants
3 Participants
n=7 Participants
2 Participants
n=5 Participants
8 Participants
n=4 Participants
Region of Enrollment
Iceland
0 Participants
n=5 Participants
3 Participants
n=7 Participants
0 Participants
n=5 Participants
3 Participants
n=4 Participants
Region of Enrollment
Italy
2 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
4 Participants
n=4 Participants
Region of Enrollment
Korea, Republic of
6 Participants
n=5 Participants
3 Participants
n=7 Participants
5 Participants
n=5 Participants
14 Participants
n=4 Participants
Region of Enrollment
New Zealand
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
2 Participants
n=4 Participants
Region of Enrollment
Poland
5 Participants
n=5 Participants
6 Participants
n=7 Participants
10 Participants
n=5 Participants
21 Participants
n=4 Participants
Region of Enrollment
Serbia
3 Participants
n=5 Participants
6 Participants
n=7 Participants
5 Participants
n=5 Participants
14 Participants
n=4 Participants
Region of Enrollment
South Africa
0 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
1 Participants
n=4 Participants
Region of Enrollment
Spain
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
2 Participants
n=4 Participants
Region of Enrollment
Ukraine
2 Participants
n=5 Participants
4 Participants
n=7 Participants
0 Participants
n=5 Participants
6 Participants
n=4 Participants
Autism Spectrum Disorder Subtype
Autism
101 Participants
n=5 Participants
99 Participants
n=7 Participants
100 Participants
n=5 Participants
300 Participants
n=4 Participants
Autism Spectrum Disorder Subtype
Asperger's Disorder
30 Participants
n=5 Participants
30 Participants
n=7 Participants
27 Participants
n=5 Participants
87 Participants
n=4 Participants
Autism Spectrum Disorder Subtype
PDD-NOS
29 Participants
n=5 Participants
31 Participants
n=7 Participants
30 Participants
n=5 Participants
90 Participants
n=4 Participants

PRIMARY outcome

Timeframe: Baseline (Visit 1) to week 12

Population: 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.)

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.

Outcome measures

Outcome measures
Measure
Placebo
n=158 Participants
Dose-matched placebo, oral administration, once per day.
Memantine Reduced Dose
n=160 Participants
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration, once per day.
Memantine Full-Dose
n=153 Participants
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg; oral administration. Once per day.
Proportion of Patients Meeting the Criterion for Loss of Therapeutic Response (LTR) by the End of the Study (Based on Observed Cases)
69.0 Percentage of patients with LTR
67.5 Percentage of patients with LTR
66.7 Percentage of patients with LTR

SECONDARY outcome

Timeframe: Baseline to week 12

Population: 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.)

Time to the first visit when a patient shows LTR following randomization to memantine or placebo.

Outcome measures

Outcome measures
Measure
Placebo
n=158 Participants
Dose-matched placebo, oral administration, once per day.
Memantine Reduced Dose
n=160 Participants
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration, once per day.
Memantine Full-Dose
n=153 Participants
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg; oral administration. Once per day.
Time to First Loss of Therapeutic (LTR) Response
29 Days
Interval 28.0 to 42.0
33 Days
Interval 28.0 to 56.0
30 Days
Interval 28.0 to 44.0

SECONDARY outcome

Timeframe: Baseline (Visit 1) to week 12

Population: 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).

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).

Outcome measures

Outcome measures
Measure
Placebo
n=154 Participants
Dose-matched placebo, oral administration, once per day.
Memantine Reduced Dose
n=159 Participants
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration, once per day.
Memantine Full-Dose
n=153 Participants
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg; oral administration. Once per day.
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Speech Subscale at Week 12
0.1 units on a scale
Standard Error 0.2
0.1 units on a scale
Standard Error 0.2
0.2 units on a scale
Standard Error 0.2

SECONDARY outcome

Timeframe: Baseline (Visit 1) to week 12

Population: 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).

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).

Outcome measures

Outcome measures
Measure
Placebo
n=154 Participants
Dose-matched placebo, oral administration, once per day.
Memantine Reduced Dose
n=159 Participants
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration, once per day.
Memantine Full-Dose
n=153 Participants
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg; oral administration. Once per day.
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Syntax Subscale at Week 12
0.0 units on a scale
Standard Error 0.2
0.3 units on a scale
Standard Error 0.2
0.1 units on a scale
Standard Error 0.2

SECONDARY outcome

Timeframe: Baseline (Visit 1) to week 12

Population: 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).

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).

Outcome measures

Outcome measures
Measure
Placebo
n=154 Participants
Dose-matched placebo, oral administration, once per day.
Memantine Reduced Dose
n=159 Participants
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration, once per day.
Memantine Full-Dose
n=153 Participants
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg; oral administration. Once per day.
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Semantics Subscale at Week 12
0.3 units on a scale
Standard Error 0.2
0.7 units on a scale
Standard Error 0.2
0.3 units on a scale
Standard Error 0.2

SECONDARY outcome

Timeframe: Baseline (Visit 1) to week 12

Population: 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).

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).

Outcome measures

Outcome measures
Measure
Placebo
n=154 Participants
Dose-matched placebo, oral administration, once per day.
Memantine Reduced Dose
n=159 Participants
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration, once per day.
Memantine Full-Dose
n=153 Participants
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg; oral administration. Once per day.
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Coherence Subscale at Week 12
0.7 units on a scale
Standard Error 0.3
1.0 units on a scale
Standard Error 0.3
1.0 units on a scale
Standard Error 0.3

SECONDARY outcome

Timeframe: Baseline (Visit 1) to week 12

Population: 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).

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).

Outcome measures

Outcome measures
Measure
Placebo
n=154 Participants
Dose-matched placebo, oral administration, once per day.
Memantine Reduced Dose
n=159 Participants
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration, once per day.
Memantine Full-Dose
n=153 Participants
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg; oral administration. Once per day.
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Initiation Subscale at Week 12
1.4 units on a scale
Standard Error 0.3
1.6 units on a scale
Standard Error 0.3
1.2 units on a scale
Standard Error 0.3

SECONDARY outcome

Timeframe: Baseline (Visit 1) to week 12

Population: 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).

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).

Outcome measures

Outcome measures
Measure
Placebo
n=154 Participants
Dose-matched placebo, oral administration, once per day.
Memantine Reduced Dose
n=159 Participants
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration, once per day.
Memantine Full-Dose
n=153 Participants
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg; oral administration. Once per day.
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Scripted Language Subscale at Week 12
0.8 units on a scale
Standard Error 0.2
1.1 units on a scale
Standard Error 0.2
0.9 units on a scale
Standard Error 0.2

SECONDARY outcome

Timeframe: Baseline (Visit 1) to week 12

Population: 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).

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).

Outcome measures

Outcome measures
Measure
Placebo
n=154 Participants
Dose-matched placebo, oral administration, once per day.
Memantine Reduced Dose
n=159 Participants
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration, once per day.
Memantine Full-Dose
n=153 Participants
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg; oral administration. Once per day.
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Context Subscale at Week 12
0.9 units on a scale
Standard Error 0.3
0.8 units on a scale
Standard Error 0.3
0.8 units on a scale
Standard Error 0.3

SECONDARY outcome

Timeframe: Baseline (Visit 1) to week 12

Population: 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).

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).

Outcome measures

Outcome measures
Measure
Placebo
n=154 Participants
Dose-matched placebo, oral administration, once per day.
Memantine Reduced Dose
n=159 Participants
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration, once per day.
Memantine Full-Dose
n=153 Participants
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg; oral administration. Once per day.
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Nonverbal Communication Subscale at Week 12
1.2 units on a scale
Standard Error 0.3
1.5 units on a scale
Standard Error 0.3
1.8 units on a scale
Standard Error 0.3

SECONDARY outcome

Timeframe: Baseline (Visit 1) to week 12

Population: 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).

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).

Outcome measures

Outcome measures
Measure
Placebo
n=154 Participants
Dose-matched placebo, oral administration, once per day.
Memantine Reduced Dose
n=159 Participants
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration, once per day.
Memantine Full-Dose
n=153 Participants
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg; oral administration. Once per day.
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Social Relations Subscale at Week 12
1.5 units on a scale
Standard Error 0.3
1.8 units on a scale
Standard Error 0.3
1.8 units on a scale
Standard Error 0.3

SECONDARY outcome

Timeframe: Baseline (Visit 1) to week 12

Population: 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).

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).

Outcome measures

Outcome measures
Measure
Placebo
n=154 Participants
Dose-matched placebo, oral administration, once per day.
Memantine Reduced Dose
n=159 Participants
Memantine, 3mg every other day, 3mg per day, or 6mg per day depending on weight group and tolerability. Oral administration, once per day.
Memantine Full-Dose
n=153 Participants
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg; oral administration. Once per day.
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Interests Subscale at Week 12
0.9 units on a scale
Standard Error 0.3
1.3 units on a scale
Standard Error 0.3
1.2 units on a scale
Standard Error 0.3

Adverse Events

Placebo

Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths

Memantine Reduced Dose

Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths

Memantine Full-Dose

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Placebo
n=160 participants at risk
Dose-matched placebo, oral administration, once per day.
Memantine Reduced Dose
n=160 participants at risk
Memantine, 3mg every other day, 3mg per day, or 6mg per day. Oral administration.
Memantine Full-Dose
n=157 participants at risk
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg; oral administration. Once per day.
Infections and infestations
Furuncle
0.00%
0/160 • 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.
Safety results are based on Safety Population (ie, all randomized patients who took at least 1 dose of double-blind study drug).
0.62%
1/160 • 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.
Safety results are based on Safety Population (ie, all randomized patients who took at least 1 dose of double-blind study drug).
0.00%
0/157 • 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.
Safety results are based on Safety Population (ie, all randomized patients who took at least 1 dose of double-blind study drug).

Other adverse events

Other adverse events
Measure
Placebo
n=160 participants at risk
Dose-matched placebo, oral administration, once per day.
Memantine Reduced Dose
n=160 participants at risk
Memantine, 3mg every other day, 3mg per day, or 6mg per day. Oral administration.
Memantine Full-Dose
n=157 participants at risk
Memantine, 3mg, 6mg, 9mg, 12mg or 15mg; oral administration. Once per day.
General disorders
Irritability
5.0%
8/160 • 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.
Safety results are based on Safety Population (ie, all randomized patients who took at least 1 dose of double-blind study drug).
3.1%
5/160 • 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.
Safety results are based on Safety Population (ie, all randomized patients who took at least 1 dose of double-blind study drug).
2.5%
4/157 • 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.
Safety results are based on Safety Population (ie, all randomized patients who took at least 1 dose of double-blind study drug).

Additional Information

Therapeutic Area Head

Allergan

Phone: 714-246-4500

Results disclosure agreements

  • Principal investigator is a sponsor employee 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.
  • Publication restrictions are in place

Restriction type: OTHER