Study of Pharmacokinetics, Safety, Efficacy, and Tolerability of Memantine in Children With Autism
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| ClinicalTrials.gov Identifier: NCT00872898 |
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Recruitment Status :
Completed
First Posted : March 31, 2009
Results First Posted : January 14, 2014
Last Update Posted : January 14, 2014
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Autism | Drug: Memantine - Extended Release (ER) Drug: Placebo | Phase 2 |
This is a multicenter, two-part study in pediatric (ages 6 to 18 years) patients diagnosed with autism.
Patients participating in Part One will receive a single open-label dose of memantine. Blood samples for pharmacokinetic analysis will be collected.
Part Two is a randomized, double-blind, placebo-controlled 12-week efficacy and safety study evaluating change in all core domains (social interactions, communication, and restricted interests and repetitive behaviors) of autism.
In the Forest autism trials conducted in children ages 6-12, dosing with an extended release formulation of memantine was weight-based. These weight based dose limits were selected to ensure exposure in terms of area under the curve (AUC) was less than the predefined limit of 2100 ng∙h/mL that represented a 10-fold lower exposure than observed at the NOAEL (No observed adverse effect level) of 15 mg/kg/day in juvenile rats.
The weight-based dose limits in these studies were as follows:
- Group A: ≥ 60 kg; max 15 mg/day
- Group B: 40-59 kg; max 9 mg/day
- Group C: 20-39 kg; max 6 mg/day
- Group D: < 20 kg; max 3 mg/day
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 124 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | An Open-label (Part One) and a Randomized, Double-blind, Placebo-Controlled (Part Two) Study of the Pharmacokinetics, Safety, Efficacy, and Tolerability of Memantine in Pediatric Patients With Autism |
| Study Start Date : | April 2009 |
| Actual Primary Completion Date : | August 2012 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: 1
Once daily oral administration of memantine for 12 weeks.
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Drug: Memantine - Extended Release (ER)
Memantine - 3mg and 6mg capsules, dose ranging 3 - 18 mg/day in 4 weight groups, administered orally.
Other Name: Namenda ER |
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Placebo Comparator: 2
Once daily oral administration of placebo for 12 weeks.
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Drug: Placebo
Placebo capsules, once daily, oral administration. |
- Extent of Absorption of Memantine (Part One) [ Time Frame: 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 [ Time Frame: 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.
- Core Autism Treatment Scale-Improvement: Total Score [ Time Frame: 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).
- Core Autism Treatment Scale-Improvement: Social Interaction [ Time Frame: 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).
- Core Autism Treatment Scale-Improvement: Communication [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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).
- Change in Children's Communication Checklist-2 (CCC-2) - Initiation Subscale [ Time Frame: 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).
- Change in Children's Communication Checklist-2 (CCC-2) - Scripted Language Subscale [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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).
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 6 Years to 18 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00872898
| United States, Arizona | |
| Forest Investigative Site | |
| Phoenix, Arizona, United States, 85006 | |
| United States, California | |
| Forest Investigative Site | |
| Sacramento, California, United States, 95817 | |
| Forest Investigative Site | |
| San Francisco, California, United States, 94143 | |
| Forest Investigative Site | |
| Santa Ana, California, United States, 92705 | |
| Forest Investigative Site | |
| Stanford, California, United States, 94305 | |
| United States, Florida | |
| Forest Investigative Site | |
| Jacksonville Beach, Florida, United States, 32250 | |
| Forest Investigative Site | |
| St Petersburg, Florida, United States, 33701 | |
| United States, Illinois | |
| Forest Investigative Site | |
| Hoffman Estates, Illinois, United States, 60169 | |
| Forest Investigative site | |
| Naperville, Illinois, United States, 60563 | |
| United States, Indiana | |
| Forest Investigative Site | |
| Indianapolis, Indiana, United States, 46202 | |
| United States, Massachusetts | |
| Forest Investigative Site | |
| Cambridge, Massachusetts, United States, 02138 | |
| United States, New Jersey | |
| Forest Investigative Site | |
| Toms River, New Jersey, United States, 08755 | |
| Forest Investigative Site | |
| Voorhees, New Jersey, United States, 08043 | |
| United States, New York | |
| Forest Investigative Site | |
| Manhasset, New York, United States, 11030 | |
| United States, Ohio | |
| Forest Investigative Site | |
| Cleveland, Ohio, United States, 44106 | |
| Forest Investigative Site | |
| Columbus, Ohio, United States, 43210 | |
| United States, Oklahoma | |
| Forest Investigative Site | |
| Oklahoma City, Oklahoma, United States, 73116 | |
| Study Director: | Ephraim Katz, PhD | Forest Research Institute, a subsidiary of Forest Laboratories, Inc. |
| Responsible Party: | Forest Laboratories |
| ClinicalTrials.gov Identifier: | NCT00872898 |
| Other Study ID Numbers: |
MEM-MD-57A |
| First Posted: | March 31, 2009 Key Record Dates |
| Results First Posted: | January 14, 2014 |
| Last Update Posted: | January 14, 2014 |
| Last Verified: | November 2013 |
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autism memantine pediatric Forest Laboratories Autism in pediatric patients |
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Autistic Disorder Autism Spectrum Disorder Child Development Disorders, Pervasive Neurodevelopmental Disorders Mental Disorders Memantine Antiparkinson Agents |
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