An Open-Label Safety Study of Memantine in Pediatric Patients With Autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS)

Autism Clinical Trial

Official title:

An Open-Label Study of the Safety and Tolerability of Memantine in Pediatric Patients With Autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01592786
• Other study ID #: MEM-MD-91
• Status: Completed
• Phase: Phase 2
• First received: May 3, 2012
• Last updated: July 15, 2014
• Start date: June 2012
• Est. completion date: August 2013

Study information

• Verified date: July 2014
• Source: Forest Laboratories
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustralia: National Health and Medical Research CouncilBelgium: Federal Agency for Medicinal Products and Health ProductsCanada: Public Health Agency of CanadaColombia: Ministry of Health and Social ProtectionEstonia: The State Agency of MedicineFrance: Ministry of HealthHungary: Research Ethics Medical CommitteeIceland: Ministry of Health and Social SecurityItaly: Ethics CommitteeNew Zealand: Ministry of HealthPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsSingapore: Ministry of HealthSouth Africa: Medicines Control CouncilSouth Korea: Korea Food and Drug Administration (KFDA)Spain: Spanish Agency of MedicinesUkraine: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and tolerability of memantine in pediatric (6-12 years old) patients with autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) and to identify responders for participation in a follow-up randomized withdrawal study.

Description:

This 50-week multicenter and multinational clinical study is comprised of a 2-week screening period, a 6-week open-label dose-titration period followed by a variable duration maintenance period (up to 42 weeks).

Patients with at least 12 weeks of investigational product exposure who meet the protocol specified responder criterion at two consecutive visits separated by at least two weeks are eligible to transition to a randomized withdrawal study. A responder is defined as a patient who demonstrates 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.

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 No observed adverse effect level (NOAEL) 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 906
• Est. completion date: August 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 12 Years

Eligibility

Inclusion Criteria:

1. Male or female outpatients.

2. Age of 6-12.

3. Meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnostic criteria for autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS)

4. 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

Exclusion Criteria:

1. Have enrolled in Study MEM-MD-57A

2. Medical conditions that might interfere with the conduct of the study, confound interpretation of the study results, or endanger the patient's well-being.

3. Participation in any other clinical investigation using an experimental drug within 30 days of screening.

4. Having any primary psychiatric (Axis I) diagnosis other than autism, Asperger's Disorder, and PDD-NOS.

5. Meeting DSM-IV-TR criteria for bipolar I disorder, psychotic disorder not otherwise specified, posttraumatic stress disorder, schizophrenia, or major depressive disorder within the past 6 months

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asperger Syndrome
• Asperger's
• Asperger's Disorder
• Autism
• Autism Spectrum Disorder (ASD)
• Autistic Disorder
• Child Development Disorders, Pervasive
• Developmental Disabilities
• Disease
• Pediatric Autism
• Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS)

Intervention

Drug:
• Memantine Hydrochloride (HCl)
Memantine extended release 3-mg capsules; the dosages studied ranged from 3 - 15 mg/day; weight based dosing in 4 weight groups; oral administration. Dosing is once daily for up to 48 weeks.

Locations

Country	Name	City	State
Australia	Forest Investigative Site 177	Camperdown	New South Wales
Belgium	Forest Investigative Site 204	Brussel
Belgium	Forest Investigative Site 203	Bruxelles
Belgium	Forest Investigative Site 202	Hoboken
Belgium	Forest Investigative Site 201	Leuven
Canada	Forest Investigative Site 155	Toronto	Ontario
Colombia	Forest Investigative Site 227	Barranquilla
Colombia	Forest Investigative Site 228	Bello
Colombia	Forest Investigative Site 226	Bogota
Estonia	Forest Investigative Site 276	Tallinn
France	Forest Investigative Site 329	Bron	Rhone
France	Forest Investigative Site 326	Paris
Hungary	Forest Investigative Site 376	Budapest
Hungary	Forest Investigative Site 378	Budapest
Hungary	Forest Investigative Site 379	Budapest
Hungary	Forest Investigative Site 381	Budapest
Hungary	Forest Investigative Site 382	Gyula
Hungary	Forest Investigative Site 380	Szeged
Iceland	Forest Investigative Site 401	Kopavogur
Italy	Forest Investigative Site 453	Roma
Italy	Forest Investigative Site 452	Siena
Korea, Republic of	Forest Investigative Site 701	Seoul
Korea, Republic of	Forest Investigative Site 702	Seoul
Korea, Republic of	Forest Investigative Site 703	Seoul
Korea, Republic of	Forest Investigative Site 704	Yangsan-si	Gyeongsangnam-do
New Zealand	Forest Investigative Site 526	Wellington
Poland	Forest Investigative Site 578	Gdansk
Poland	Forest Investigative Site 579	Gdansk
Poland	Forest Investigative Site 580	Kielce
Poland	Forest Investigative Site 576	Kobierzyce
Poland	Forest Investigative Site 577	Warszawa
Serbia	Forest Investigative Site 626	Belgrade
Serbia	Forest Investigative Site 627	Belgrade
Serbia	Forest Investigative Site 629	Nis
Serbia	Forest Investigative Site 628	Novi Sad
Singapore	Forest Investigative Site 651	Singapore
South Africa	Forest Investigative Site 676	Cape Town	Western Cape
Spain	Forest Investigative Site 729	Barcelona
Spain	Forest Investigative Site 727	Madrid
Spain	Forest Investigative Site 728	Sabadell	Barcelona
Spain	Forest Investigative Site 730	Torremolinos	Málaga
Ukraine	Forest Investigative Site 803	Donetsk
Ukraine	Forest Investigative Site 807	Kharkiv
Ukraine	Forest Investigative Site 802	Kherson	Vil. Stepanivka
Ukraine	Forest Investigative Site 804	Kyiv
Ukraine	Forest Investigative Site 801	Odesa
United States	Forest Investigative Site 081	Albuquerque	New Mexico
United States	Forest Investigative Site 107	Albuquerque	New Mexico
United States	Forest Investigative Site 069	Avon Lake	Ohio
United States	Forest Investigative Site 071	Bothell	Washington
United States	Forest Investigative Site 078	Boulder	Colorado
United States	Forest Investigative Site 075	Bradenton	Florida
United States	Forest Investigative Site 098	Bronx	New York
United States	Forest Investigative Site 073	Centennial	Colorado
United States	Forest Investigative Site 072	Chapel Hill	North Carolina
United States	Forest Investigative Site 105	Charleston	South Carolina
United States	Forest Investigative Site 119	Charleston	West Virginia
United States	Forest Investigative Site 064	Charlottesville	Virginia
United States	Forest Investigative Site 028	Clinton	Utah
United States	Forest Investigative Site 001	Columbus	Ohio
United States	Forest Investigative Site 068	Dothan	Alabama
United States	Forest Investigative Site 082	Evansville	Indiana
United States	Forest Investigative Site 123	Fort Wayne	Indiana
United States	Forest Investigative Site 080	Gainesville	Florida
United States	Forest Investigative Site 054	Glendale	California
United States	Forest Investigative Site 053	Gresham	Oregon
United States	Forest Investigative Site 130	Henderson	Nevada
United States	Forest Investigative Site 051	Houston	Texas
United States	Forest Investigative Site 109	Imperial	California
United States	Forest Investigative Site 056	Indianapolis	Indiana
United States	Forest Investigative Site 084	Indianapolis	Indiana
United States	Forest Investigative Site 066	Irvine	California
United States	Forest Investigative Site 117	Jacksonville	Florida
United States	Forest Investigative Site 132	Johnstown	Pennsylvania
United States	Forest Investigative Site 095	Lake Charles	Louisiana
United States	Forest Investigative Site 104	Las Vegas	Nevada
United States	Forest Investigative Site 102	Libertyville	Illinois
United States	Forest Investigative Site 097	Lincoln	Nebraska
United States	Forest Investigative Site 116	Lincoln	Nebraska
United States	Forest Investigative Site 077	Little Rock	Arkansas
United States	Forest Investigative Site 096	Los Angeles	California
United States	Forest Investigative Site 061	Louisville	Kentucky
United States	Forest Investigative Site 065	Maitland	Florida
United States	Forest Investigative Site 131	McMurray	Pennsylvania
United States	Forest Investigative Site 100	Media	Pennsylvania
United States	Forest Investigative Site 090	Memphis	Tennessee
United States	Forest Investigative Site 118	Miami	Florida
United States	Forest Investigative Site 063	Middleton	Wisconsin
United States	Forest Investigative Site 023	Naperville	Illinois
United States	Forest Investigative Site 057	Nashville	Tennessee
United States	Forest Investigative Site 136	Neptune	New Jersey
United States	Forest Investigative Site 091	New Orleans	Louisiana
United States	Forest Investigative Site 059	Newton	Massachusetts
United States	Forest Investigative Site 113	Norfolk	Virginia
United States	Forest Investigative Site 085	Oakland Park	Florida
United States	Forest Investigative Site 141	Ogden	Utah
United States	Forest Investigative Site 019	Oklahoma City	Oklahoma
United States	Forest Investigative Site 115	Orange City	Florida
United States	Forest Investigative Site 062	Orlando	Florida
United States	Forest Investigative Site 114	Orlando	Florida
United States	Forest Investigative Site 124	Orlando	Florida
United States	Forest Investigative Site 125	Orlando	Florida
United States	Forest Investigative Site 074	Owensboro	Kentucky
United States	Forest Investigative Site 005	Phoenix	Arizona
United States	Forest Investigative Site 086	Rockville	Maryland
United States	Forest Investigative Site 029	Salt Lake City	Utah
United States	Forest Investigative Site 021	San Francisco	California
United States	Forest Investigative Site 026	Santa Ana	California
United States	Forest Investigative Site 108	Springfield	Massachusetts
United States	Forest Investigative Site 002	Stanford	California
United States	Forest Investigative Site 067	Tampa	Florida
United States	Forest Investigative Site 070	The Woodlands	Texas
United States	Forest Investigative Site 127	Toms River	New Jersey
United States	Forest Investigative Site 055	Tucson	Arizona
United States	Forest Investigative Site 092	Tulsa	Oklahoma
United States	Forest Investigative Site 052	Washington	District of Columbia
United States	Forest Investigative Site 101	Wellington	Florida
United States	Forest Investigative Site 106	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Forest Laboratories

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Colombia,  Estonia,  France,  Hungary,  Iceland,  Italy,  Korea, Republic of,  New Zealand,  Poland,  Serbia,  Singapore,  South Africa,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Confirmed Social Responsiveness Scale (SRS) Responders	A confirmed SRS responder was defined as a patient who had at least 12 weeks of exposure to memantine, and a = 10-point reduction in the SRS total raw score relative to baseline at 2 consecutive visits separated by at least 2 weeks.; The SRS is a 65-item, caregiver-rated assessment scale that measures observable items on social behavior and social language use, as well as characteristics of autism in a naturalistic social setting. Each item is rated on a scale from 0 (never true) to 3 (almost always true). The SRS total raw score ranges from 0 to 195; a higher score indicates greater severity of social impairment.	Visit 1 (Baseline) to Visit 8 (week 48/Final Visit)	No