Withdrawal Study of Memantine in Pediatric Patients With Autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified Previously Treated With Memantine

NCT ID: NCT01592747

Last Updated: 2019-04-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 479 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2013-10-31

Brief Summary

The purpose of this randomized withdrawal study is to evaluate the safety, tolerability, and efficacy of memantine compared with placebo in pediatric patients with autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS).

Detailed Description

This clinical study was a 12-week, multicenter, double-blind, placebo-controlled, randomized withdrawal study in pediatric outpatients with autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS). Patients who completed at least 12 weeks of study drug exposure and met protocol specified responder criterion in lead in Study MEM-MD-91 (NCT01592786) at two consecutive visits separated by at least two weeks were eligible to transition to this study. The responder criterion was defined as having at least a 10 point improvement (reduction in score) in the Social Responsiveness Scale (SRS) total raw score relative to the Visit 1 total raw score in Study MEM-MD-91.

Weight based dose limits were selected in this study to ensure that exposure in terms of area under the curve (AUC) was less than the predefined limit of 2100 ng·h/mL which represents 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 this study were as follows:

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

Conditions

Autistic Disorder; Autism; Asperger's Disorder; Asperger Syndrome; Autism Spectrum Disorders; Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Memantine 1

Patients randomized to the full dose arm will continue taking memantine at the same tolerability and weight-based dose achieved in lead-in Study MEM-MD-91. Dosing will be once daily for up to 12 weeks.

Group Type: EXPERIMENTAL

Memantine Hydrochloride (HCl)

Intervention Type: DRUG

Extended Release Dose ranging from 3-15mg/day; administered orally

Memantine 2

Patients randomized to the reduced dose arm will take memantine at the tolerability and weight based dose that they received in lead in Study MEM-MD-91 reduced by at least 50%. Dosing will be once daily for up to 12 weeks.

Group Type: EXPERIMENTAL

Memantine Hydrochloride (HCl)

Intervention Type: DRUG

Extended Release Dose ranging from 3mg every other day to 6mg/day; administered orally.

Placebo

Dosing will be once daily for up to 12 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo capsules

Intervention Type: DRUG

Once daily, oral administration.

Interventions

Memantine Hydrochloride (HCl)

Extended Release Dose ranging from 3-15mg/day; administered orally

Intervention Type: DRUG

Memantine Hydrochloride (HCl)

Extended Release Dose ranging from 3mg every other day to 6mg/day; administered orally.

Intervention Type: DRUG

Placebo capsules

Once daily, oral administration.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Completed at least 12 weeks of exposure to study drug in lead-in study MEM-MD-91 (NCT01592786)

2. Met responder criterion at two consecutive visits separated by at least two weeks in lead-in study MEM-MD-91

3. Provide written informed assent, when developmentally appropriate, to participate in the study before conduct of any study-specific procedures. The parent/guardian/LAR must provide written informed consent before the patient's participation in the study. A separate written informed consent for the caregiver must also be obtained before the conduct of any study specific procedures

4. Have a knowledgeable caregiver who is capable of providing reliable information about the patient's condition, attending all clinic visits with the patient, and overseeing the administration of study drug. Every effort should be made to maintain the same caregiver as used in the lead-in study throughout this study

5. Have normal results from the physical examination, laboratory tests, ECG, and vital signs at Visit 1 of this study (last visit of Study MEM-MD-91). Any abnormal findings must be deemed not clinically significant by the Investigator and documented

6. Be able to speak and understand English sufficiently (or their native language if this can be accommodated by the site), as well as have a caregiver and parent/guardian/LAR who is able to speak and understand English sufficiently (or their native language if this can be accommodated by the site), to comprehend the nature of the study and to allow for the completion of all study assessments

7. Have a family that is sufficiently organized and stable to guarantee adequate safety monitoring and continuous attendance to clinic visits for the duration of the study

8. Females who are 9 years and older or who have had onset of menses must have a negative urine pregnancy test at Visit 1

9. Age of 6 years to 12 years at the time of entry into lead in study MEM-MD-91

Exclusion Criteria

1. Patients with a concurrent medical condition that might interfere with the conduct of the study, confound interpretation of the study results, or endanger the patient's well being

2. Significant risk of suicidality based on the Investigator's judgment, the Aberrant Behavior Checklist-Irritability subscale (ABC-I), or if appropriate, as indicated by a response of "yes" to questions 4 or 5 in the suicidal ideation section of the Children's C-SSRS (Columbia-Suicide Severity Rating Scale) or any suicidal behavior.

3. Patients with evidence or history of malignancy (other than excised basal cell carcinoma) or any significant hematologic, endocrine, cardiovascular (including any rhythm disorder), neurologic, respiratory, renal, hepatic, or gastrointestinal disease

4. Female patients of child-bearing potential who are not using or not willing to use a conventional method of contraception approved by the PI. Abstinence is an acceptable method of contraception

5. Patients requiring treatment with prohibited concomitant medications

6. Patients who, in the opinion of the Investigator, might not be suitable for the study

7. Employee or immediate relative of an employee of Forest Laboratories, Inc., any of its affiliates or partners, or the study center

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Forest Laboratories

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jordan Lateiner, MS, MBA

Role: STUDY_DIRECTOR

Forest Research Institute, Inc.- A Subsidiary of Forest Laboratories, Inc.

Locations

Forest Investigative Site 068

Dothan, Alabama, United States

Forest Investigative Site 005

Phoenix, Arizona, United States

Forest Investigative Site 055

Tucson, Arizona, United States

Forest Investigative Site 077

Little Rock, Arkansas, United States

Forest Investigative Site 054

Glendale, California, United States

Forest Investigative Site 109

Imperial, California, United States

Forest Investigative Site 096

Los Angeles, California, United States

Forest Investigative Site 021

San Francisco, California, United States

Forest Investigative Site 026

Santa Ana, California, United States

Forest Investigative Site 002

Stanford, California, United States

Forest Investigative Site 078

Boulder, Colorado, United States

Forest Investigative Site 073

Centennial, Colorado, United States

Forest Investigative Site 052

Washington D.C., District of Columbia, United States

Forest Investigative Site 075

Bradenton, Florida, United States

Forest Investigative Site 080

Gainesville, Florida, United States

Forest Investigative Site 117

Jacksonville, Florida, United States

Forest Investigative Site 065

Maitland, Florida, United States

Forest Investigative Site 118

Miami, Florida, United States

Forest Investigative Site 085

Oakland Park, Florida, United States

Forest Investigative Site 115

Orange City, Florida, United States

Forest Investigative Site 125

Orlando, Florida, United States

Forest Investigative Site 062

Orlando, Florida, United States

Forest Investigative Site 067

Tampa, Florida, United States

Forest Investigative Site 101

Wellington, Florida, United States

Forest Investigative Site 102

Libertyville, Illinois, United States

Forest Investigative Site 023

Naperville, Illinois, United States

Forest Investigative Site 082

Evansville, Indiana, United States

Forest Investigative Site 056

Indianapolis, Indiana, United States

Forest Investigative Site 106

Wichita, Kansas, United States

Forest Investigative Site 061

Louisville, Kentucky, United States

Forest Investigative Site 095

Lake Charles, Louisiana, United States

Forest Investigative Site 086

Rockville, Maryland, United States

Forest Investigative Site 059

Newton, Massachusetts, United States

Forest Investigative Site 108

Springfield, Massachusetts, United States

Forest Investigative Site 116

Lincoln, Nebraska, United States

Forest Investigative Site 097

Lincoln, Nebraska, United States

Forest Investigative Site 130

Henderson, Nevada, United States

Forest Investigative Site 104

Las Vegas, Nevada, United States

Forest Investigative Site 136

Neptune City, New Jersey, United States

Forest Investigative Site 127

Toms River, New Jersey, United States

Forest Investigative Site 081

Albuquerque, New Mexico, United States

Forest Investigative Site 107

Albuquerque, New Mexico, United States

Forest Investigative Site 072

Chapel Hill, North Carolina, United States

Forest Investigative Site 069

Avon Lake, Ohio, United States

Forest Investigative Site 001

Columbus, Ohio, United States

Forest Investigative Site 019

Oklahoma City, Oklahoma, United States

Forest Investigative Site 092

Tulsa, Oklahoma, United States

Forest Investigative Site 053

Gresham, Oregon, United States

Forest Investigative Site 132

Johnstown, Pennsylvania, United States

Forest Investigative Site 131

McMurray, Pennsylvania, United States

Forest Investigative Site 100

Media, Pennsylvania, United States

Forest Investigative Site 105

Charleston, South Carolina, United States

Forest Investigative Site 090

Memphis, Tennessee, United States

Forest Investigative Site 057

Nashville, Tennessee, United States

Forest Investigative Site 051

Houston, Texas, United States

Forest Investigative Site 070

The Woodlands, Texas, United States

Forest Investigative Site 028

Clinton, Utah, United States

Forest Investigative Site 141

Ogden, Utah, United States

Forest Investigative Site 029

Salt Lake City, Utah, United States

Forest Investigative Site 064

Charlottesville, Virginia, United States

Forest Investigative Site 113

Norfolk, Virginia, United States

Forest Investigative Site 071

Bothell, Washington, United States

Forest Investigative Site 119

Charleston, West Virginia, United States

Forest Investigative Site 063

Middleton, Wisconsin, United States

Forest Investigative Site 204

Brussels, , Belgium

Forest Investigative Site 203

Brussels, , Belgium

Forest Investigative Site 228

Bello, , Colombia

Forest Investigative Site 226

Bogotá, , Colombia

Forest Investigative Site 276

Tallinn, , Estonia

Forest Investigative Site 329

Bron, , France

Forest Investigative Site 381

Budapest, , Hungary

Forest Investigative Site 376

Budapest, , Hungary

Forest Investigative Site 378

Budapest, , Hungary

Forest Investigative Site 401

Kopavogur, , Iceland

Forest Investigative Site 453

Roma, , Italy

Forest Investigative Site 452

Siena, , Italy

Forest Investigative Site 526

Wellington, , New Zealand

Forest Investigative Site 579

Gdansk, , Poland

Forest Investigative Site 578

Gdansk, , Poland

Forest Investigative Site 576

Kobierzyce, , Poland

Forest Investigative Site 577

Warsaw, , Poland

Forest Investigative Site 626

Belgrade, , Serbia

Forest Investigative Site 627

Belgrade, , Serbia

Forest Investigative Site 629

Niš, , Serbia

Forest Investigative Site 628

Novi Sad, , Serbia

Forest Investigative Site 676

Cape Town, Western Cape, South Africa

Forest Investigative Site 704

Yangsan, Gyeongsangnam-do, South Korea

Forest Investigative Site 702

Seoul, , South Korea

Forest Investigative Site 703

Seoul, , South Korea

Forest Investigative Site 701

Seoul, , South Korea

Forest Investigative Site 728

Sabadell, Barcelona, Spain

Forest Investigative Site 807

Kharkiv, , Ukraine

Forest Investigative Site 802

Kherson,Vil. Stepanivka, , Ukraine

Forest Investigative Site 804

Kyiv, , Ukraine

Countries

United States; Belgium; Colombia; Estonia; France; Hungary; Iceland; Italy; New Zealand; Poland; Serbia; South Africa; South Korea; Spain; Ukraine

References

Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.

Reference Type: DERIVED

PMID: 37811711 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36006807 (View on PubMed)

Other Identifiers

MEM-MD-68

Identifier Type: -

Identifier Source: org_study_id