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

November 26, 2013 updated by: Forest Laboratories

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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

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

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

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

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

  • Group A: ≥ 60 kg; max 15 mg/day
  • Group B: 40-59 kg; max 9 mg/day
  • Group C: 20-39 kg; max 6 mg/day
  • Group D: < 20 kg; max 3 mg/day

Study Type

Interventional

Enrollment (Actual)

124

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85006
        • Forest Investigative Site
    • California
      • 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
        • Forest Investigative Site
    • Florida
      • Jacksonville Beach, Florida, United States, 32250
        • Forest Investigative Site
      • St Petersburg, Florida, United States, 33701
        • Forest Investigative Site
    • Illinois
      • Hoffman Estates, Illinois, United States, 60169
        • Forest Investigative Site
      • Naperville, Illinois, United States, 60563
        • Forest Investigative Site
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Forest Investigative Site
    • Massachusetts
      • Cambridge, Massachusetts, United States, 02138
        • Forest Investigative Site
    • New Jersey
      • Toms River, New Jersey, United States, 08755
        • Forest Investigative Site
      • Voorhees, New Jersey, United States, 08043
        • Forest Investigative Site
    • New York
      • Manhasset, New York, United States, 11030
        • Forest Investigative Site
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Forest Investigative Site
      • Columbus, Ohio, United States, 43210
        • Forest Investigative Site
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73116
        • Forest Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Once daily oral administration of memantine for 12 weeks.
Drug: Memantine - Extended Release (ER)
Memantine - 3mg and 6mg capsules, dose ranging 3 - 18 mg/day in 4 weight groups, administered orally.
Other Names:
  • Namenda ER
Placebo Comparator: 2
Once daily oral administration of placebo for 12 weeks.
Drug: Placebo
Placebo capsules, once daily, oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline to 144 hours. Measurements were taken 0 (predose), 4, 8, 24, 30, 48, 96 and 144 hours post-dose
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.
From Baseline to Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
At Week 12
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).
At Week 12
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).
At Week 12
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).
From Baseline to Week 12
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).
From Baseline to Week 12
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).
From Baseline to Week 12
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).
From Baseline to Week 12
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).
From Baseline to Week 12
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).
From Baseline to Week 12
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).
From Baseline to Week 12
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).
From Baseline to Week 12
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).
From Baseline to Week 12
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).
From Baseline to Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Forest Laboratories

Collaborators

Merz Pharmaceuticals GmbH

Investigators

  • Study Director: Ephraim Katz, PhD, Forest Research Institute, a Subsidiary of Forest Laboratories, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2009

Primary Completion (Actual)

August 1, 2012

Study Registration Dates

First Submitted

March 30, 2009

First Submitted That Met QC Criteria

March 30, 2009

First Posted (Estimate)

March 31, 2009

Study Record Updates

Last Update Posted (Estimate)

January 14, 2014

Last Update Submitted That Met QC Criteria

November 26, 2013

Last Verified

November 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MEM-MD-57A

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe