Clinical trial NCT00872898: Study of Pharmacokinetics, Safety, Efficacy, and Tolerability of Memantine in Children With Autism
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Autism
Keywords: autism
memantine
pediatric
Forest Laboratories
Autism in pediatric patients
Lead sponsor: Forest Laboratories
Sponsor class: INDUSTRY
Collaborators: name: Merz Pharmaceuticals GmbH
First posted: 2009-03-31
Enrollment: 124
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Extent of Absorption of Memantine (Part One)
timeFrame: Baseline to 144 hours. Measurements were taken 0 (predose), 4, 8, 24, 30, 48, 96 and 144 hours post-dose
measure: Change in Total Raw Score of Social Responsiveness Scale
timeFrame: From Baseline to Week 12
Secondary outcomes:
measure: Core Autism Treatment Scale-Improvement: Total Score
timeFrame: At Week 12
measure: Core Autism Treatment Scale-Improvement: Social Interaction
timeFrame: At Week 12
measure: Core Autism Treatment Scale-Improvement: Communication
timeFrame: At Week 12
measure: Change in Children's Communication Checklist-2 (CCC-2) - Speech Subscale
timeFrame: From Baseline to Week 12
measure: Change in Children's Communication Checklist-2 (CCC-2) - Syntax Subscale
timeFrame: From Baseline to Week 12
measure: Change in Children's Communication Checklist-2 (CCC-2) - Semantics Subscale
timeFrame: From Baseline to Week 12
measure: Change in Children's Communication Checklist-2 (CCC-2) - Coherence Subscale
timeFrame: From Baseline to Week 12
measure: Change in Children's Communication Checklist-2 (CCC-2) - Initiation Subscale
timeFrame: From Baseline to Week 12
measure: Change in Children's Communication Checklist-2 (CCC-2) - Scripted Language Subscale
timeFrame: From Baseline to Week 12
measure: Change in Children's Communication Checklist-2 (CCC-2) - Context Subscale
timeFrame: From Baseline to Week 12
measure: Change in Children's Communication Checklist-2 (CCC-2) - Nonverbal Communication Subscale
timeFrame: From Baseline to Week 12
measure: Change in Children's Communication Checklist-2 (CCC-2) - Social Relations Subscale
timeFrame: From Baseline to Week 12
measure: Change in Children's Communication Checklist-2 (CCC-2) - Interests Subscale
timeFrame: From Baseline to Week 12
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Forest Investigative Site
state: Arizona
city: Sacramento
country: United States
facility: Forest Investigative Site
state: California
city: San Francisco
country: United States
facility: Forest Investigative Site
state: California
city: Santa Ana
country: United States
facility: Forest Investigative Site
state: California
city: Stanford
country: United States
facility: Forest Investigative Site
state: California
city: Jacksonville Beach
country: United States
facility: Forest Investigative Site
state: Florida
city: St Petersburg
country: United States
facility: Forest Investigative Site
state: Florida
city: Hoffman Estates
country: United States
facility: Forest Investigative Site
state: Illinois
city: Naperville
country: United States
facility: Forest Investigative site
state: Illinois
city: Indianapolis
country: United States
facility: Forest Investigative Site
state: Indiana
city: Cambridge
country: United States
facility: Forest Investigative Site
state: Massachusetts
city: Toms River
country: United States
facility: Forest Investigative Site
state: New Jersey
city: Voorhees
country: United States
facility: Forest Investigative Site
state: New Jersey
city: Manhasset
country: United States
facility: Forest Investigative Site
state: New York
city: Cleveland
country: United States
facility: Forest Investigative Site
state: Ohio
city: Columbus
country: United States
facility: Forest Investigative Site
state: Ohio
city: Oklahoma City
country: United States
facility: Forest Investigative Site
state: Oklahoma
Study officials:
affiliation: Forest Research Institute, a subsidiary of Forest Laboratories, Inc.
name: Ephraim Katz, PhD
role: STUDY_DIRECTOR
References:
citation: Brignell A, Marraffa C, Williams K, May T. Memantine for autism spectrum disorder. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013845. doi: 10.1002/14651858.CD013845.pub2.