Study of Pharmacokinetics, Safety, Efficacy, and Tolerability of Memantine in Children With Autism

This study has been completed.
Sponsor:
Collaborator:
Merz Pharmaceuticals GmbH
Information provided by (Responsible Party):
Forest Laboratories
ClinicalTrials.gov Identifier:
NCT00872898
First received: March 30, 2009
Last updated: November 26, 2013
Last verified: November 2013

March 30, 2009
November 26, 2013
April 2009
August 2012   (final data collection date for primary outcome measure)
  • 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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]

    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.

Change in Social Responsiveness Scale [ Time Frame: Baseline, 6 weeks after baseline, end of treatment ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00872898 on ClinicalTrials.gov Archive Site
  • Core Autism Treatment Scale-Improvement: Total Score [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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 Core Autism Treatment Scale-Improvement and Children's Communication Checklist. [ Time Frame: Baseline and every 2 weeks to end of treatment ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Study of Pharmacokinetics, Safety, Efficacy, and Tolerability of Memantine in Children With Autism
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

The purpose of this study is to investigate the safety and efficacy of memantine extended release, as well as its extent of absorption in pediatric patients with autism.

This is a multicenter, two-part study in pediatric (ages 6 to 18 years) patients diagnosed with autism.

Patients participating in Part One will receive a single open-label dose of memantine. Blood samples for pharmacokinetic analysis will be collected.

Part Two is a randomized, double-blind, placebo-controlled 12-week efficacy and safety study evaluating change in all core domains (social interactions, communication, and restricted interests and repetitive behaviors) of autism.

In the Forest autism trials conducted in children ages 6-12, dosing with an extended release formulation of memantine was weight-based. These weight based dose limits were selected to ensure exposure in terms of area under the curve (AUC) was less than the predefined limit of 2100 ng∙h/mL that represented a 10-fold lower exposure than observed at the NOAEL (No observed adverse effect level) of 15 mg/kg/day in juvenile rats.

The weight-based dose limits in these studies were as follows:

  • Group A: ≥ 60 kg; max 15 mg/day
  • Group B: 40-59 kg; max 9 mg/day
  • Group C: 20-39 kg; max 6 mg/day
  • Group D: < 20 kg; max 3 mg/day
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Autism
  • 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
  • Drug: Placebo
    Placebo capsules, once daily, oral administration.
  • Experimental: 1
    Once daily oral administration of memantine for 12 weeks.
    Intervention: Drug: Memantine - Extended Release (ER)
  • Placebo Comparator: 2
    Once daily oral administration of placebo for 12 weeks.
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
124
Not Provided
August 2012   (final data collection date for primary outcome measure)

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
Both
6 Years to 18 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00872898
MEM-MD-57A
No
Forest Laboratories
Forest Laboratories
Merz Pharmaceuticals GmbH
Study Director: Ephraim Katz, PhD Forest Research Institute, a subsidiary of Forest Laboratories, Inc.
Forest Laboratories
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP