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

Autism Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00872898
• Other study ID #: MEM-MD-57A
• Status: Completed
• Phase: Phase 2
• First received: March 30, 2009
• Last updated: November 26, 2013
• Start date: April 2009

Study information

• Verified date: November 2013
• Source: Forest Laboratories
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 18 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Autism
• Autistic Disorder

Intervention

Drug:
• Memantine - Extended Release (ER)
Memantine - 3mg and 6mg capsules, dose ranging 3 - 18 mg/day in 4 weight groups, administered orally.
• Placebo
Placebo capsules, once daily, oral administration.

Locations

Country	Name	City	State
United States	Forest Investigative Site	Cambridge	Massachusetts
United States	Forest Investigative Site	Cleveland	Ohio
United States	Forest Investigative Site	Columbus	Ohio
United States	Forest Investigative Site	Hoffman Estates	Illinois
United States	Forest Investigative Site	Indianapolis	Indiana
United States	Forest Investigative Site	Jacksonville Beach	Florida
United States	Forest Investigative Site	Manhasset	New York
United States	Forest Investigative site	Naperville	Illinois
United States	Forest Investigative Site	Oklahoma City	Oklahoma
United States	Forest Investigative Site	Phoenix	Arizona
United States	Forest Investigative Site	Sacramento	California
United States	Forest Investigative Site	San Francisco	California
United States	Forest Investigative Site	Santa Ana	California
United States	Forest Investigative Site	St Petersburg	Florida
United States	Forest Investigative Site	Stanford	California
United States	Forest Investigative Site	Toms River	New Jersey
United States	Forest Investigative Site	Voorhees	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
Forest Laboratories	Merz Pharmaceuticals GmbH

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Extent of Absorption of Memantine (Part One)	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	Yes
Primary	Change in Total Raw Score of Social Responsiveness Scale	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	No
Secondary	Core Autism Treatment Scale-Improvement: Total Score	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	No
Secondary	Core Autism Treatment Scale-Improvement: Social Interaction	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	No
Secondary	Core Autism Treatment Scale-Improvement: Communication	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	No
Secondary	Change in Children's Communication Checklist-2 (CCC-2) - Speech Subscale	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	No
Secondary	Change in Children's Communication Checklist-2 (CCC-2) - Syntax Subscale	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	No
Secondary	Change in Children's Communication Checklist-2 (CCC-2) - Semantics Subscale	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	No
Secondary	Change in Children's Communication Checklist-2 (CCC-2) - Coherence Subscale	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	No
Secondary	Change in Children's Communication Checklist-2 (CCC-2) - Initiation Subscale	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	No
Secondary	Change in Children's Communication Checklist-2 (CCC-2) - Scripted Language Subscale	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	No
Secondary	Change in Children's Communication Checklist-2 (CCC-2) - Context Subscale	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	No
Secondary	Change in Children's Communication Checklist-2 (CCC-2) - Nonverbal Communication Subscale	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	No
Secondary	Change in Children's Communication Checklist-2 (CCC-2) - Social Relations Subscale	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	No
Secondary	Change in Children's Communication Checklist-2 (CCC-2) - Interests Subscale	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	No