An Open-Label Safety Study of Memantine in Pediatric Patients With Autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS)
- Conditions
- AutismAsperger's DisorderAutistic DisorderPediatric AutismAsperger'sAutism Spectrum Disorder (ASD)Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS)
- Interventions
- Registration Number
- NCT01592786
- Lead Sponsor
- Forest Laboratories
- Brief 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.
- Detailed 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 & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 906
- Male or female outpatients.
- Age of 6-12.
- 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)
- 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
- Have enrolled in Study MEM-MD-57A
- Medical conditions that might interfere with the conduct of the study, confound interpretation of the study results, or endanger the patient's well-being.
- Participation in any other clinical investigation using an experimental drug within 30 days of screening.
- Having any primary psychiatric (Axis I) diagnosis other than autism, Asperger's Disorder, and PDD-NOS.
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Memantine Hydrochloride (HCl) Memantine Hydrochloride (HCl) Once daily oral administration of open-label memantine for up to 48 weeks: 6-week dose-titration period followed by up to 42-week maintenance period.
- Primary Outcome Measures
Name Time Method Number of Confirmed Social Responsiveness Scale (SRS) Responders Visit 1 (Baseline) to Visit 8 (week 48/Final Visit) 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (118)
Forest Investigative Site 054
🇺🇸Glendale, California, United States
Forest Investigative Site 109
🇺🇸Imperial, California, United States
Forest Investigative Site 068
🇺🇸Dothan, Alabama, United States
Forest Investigative Site 026
🇺🇸Santa Ana, California, United States
Forest Investigative Site 077
🇺🇸Little Rock, Arkansas, United States
Forest Investigative Site 102
🇺🇸Libertyville, Illinois, United States
Forest Investigative Site 023
🇺🇸Naperville, Illinois, United States
Forest Investigative Site 177
🇦🇺Camperdown, New South Wales, Australia
Forest Investigative Site 081
🇺🇸Albuquerque, New Mexico, United States
Forest Investigative Site 002
🇺🇸Stanford, California, United States
Forest Investigative Site 075
🇺🇸Bradenton, Florida, United States
Forest Investigative Site 078
🇺🇸Boulder, Colorado, United States
Forest Investigative Site 082
🇺🇸Evansville, Indiana, United States
Forest Investigative Site 071
🇺🇸Bothell, Washington, United States
Forest Investigative Site 123
🇺🇸Fort Wayne, Indiana, United States
Forest Investigative Site 098
🇺🇸Bronx, New York, United States
Forest Investigative Site 069
🇺🇸Avon Lake, Ohio, United States
Forest Investigative Site 070
🇺🇸The Woodlands, Texas, United States
Forest Investigative Site 051
🇺🇸Houston, Texas, United States
Forest Investigative Site 113
🇺🇸Norfolk, Virginia, United States
Forest Investigative Site 382
🇭🇺Gyula, Hungary
Forest Investigative Site 379
🇭🇺Budapest, Hungary
Forest Investigative Site 727
🇪🇸Madrid, Spain
Forest Investigative Site 329
🇫🇷Bron, Rhone, France
Forest Investigative Site 729
🇪🇸Barcelona, Spain
Forest Investigative Site 055
🇺🇸Tucson, Arizona, United States
Forest Investigative Site 115
🇺🇸Orange City, Florida, United States
Forest Investigative Site 101
🇺🇸Wellington, Florida, United States
Forest Investigative Site 086
🇺🇸Rockville, Maryland, United States
Forest Investigative Site 095
🇺🇸Lake Charles, Louisiana, United States
Forest Investigative Site 116
🇺🇸Lincoln, Nebraska, United States
Forest Investigative Site 059
🇺🇸Newton, Massachusetts, United States
Forest Investigative Site 108
🇺🇸Springfield, Massachusetts, United States
Forest Investigative Site 127
🇺🇸Toms River, New Jersey, United States
Forest Investigative Site 130
🇺🇸Henderson, Nevada, United States
Forest Investigative Site 136
🇺🇸Neptune, New Jersey, United States
Forest Investigative Site 090
🇺🇸Memphis, Tennessee, United States
Forest Investigative Site 141
🇺🇸Ogden, Utah, United States
Forest Investigative Site 028
🇺🇸Clinton, Utah, United States
Forest Investigative Site 073
🇺🇸Centennial, Colorado, United States
Forest Investigative Site 155
🇨🇦Toronto, Ontario, Canada
Forest Investigative Site 204
🇧🇪Brussel, Belgium
Forest Investigative Site 226
🇨🇴Bogota, Colombia
Forest Investigative Site 203
🇧🇪Bruxelles, Belgium
Forest Investigative Site 228
🇨🇴Bello, Colombia
Forest Investigative Site 202
🇧🇪Hoboken, Belgium
Forest Investigative Site 201
🇧🇪Leuven, Belgium
Forest Investigative Site 276
🇪🇪Tallinn, Estonia
Forest Investigative Site 381
🇭🇺Budapest, Hungary
Forest Investigative Site 702
🇰🇷Seoul, Korea, Republic of
Forest Investigative Site 703
🇰🇷Seoul, Korea, Republic of
Forest Investigative Site 526
🇳🇿Wellington, New Zealand
Forest Investigative Site 579
🇵🇱Gdansk, Poland
Forest Investigative Site 578
🇵🇱Gdansk, Poland
Forest Investigative Site 676
🇿🇦Cape Town, Western Cape, South Africa
Forest Investigative Site 802
🇺🇦Kherson, Vil. Stepanivka, Ukraine
Forest Investigative Site 803
🇺🇦Donetsk, Ukraine
Forest Investigative Site 804
🇺🇦Kyiv, Ukraine
Forest Investigative Site 132
🇺🇸Johnstown, Pennsylvania, United States
Forest Investigative Site 100
🇺🇸Media, Pennsylvania, United States
Forest Investigative Site 052
🇺🇸Washington, District of Columbia, 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 096
🇺🇸Los Angeles, California, United States
Forest Investigative Site 066
🇺🇸Irvine, California, United States
Forest Investigative Site 074
🇺🇸Owensboro, Kentucky, United States
Forest Investigative Site 001
🇺🇸Columbus, Ohio, United States
Forest Investigative Site 107
🇺🇸Albuquerque, New Mexico, United States
Forest Investigative Site 064
🇺🇸Charlottesville, Virginia, United States
Forest Investigative Site 106
🇺🇸Wichita, Kansas, United States
Forest Investigative Site 131
🇺🇸McMurray, Pennsylvania, United States
Forest Investigative Site 053
🇺🇸Gresham, Oregon, United States
Forest Investigative Site 092
🇺🇸Tulsa, Oklahoma, United States
Forest Investigative Site 119
🇺🇸Charleston, West Virginia, United States
Forest Investigative Site 063
🇺🇸Middleton, Wisconsin, United States
Forest Investigative Site 453
🇮🇹Roma, Italy
Forest Investigative Site 577
🇵🇱Warszawa, Poland
Forest Investigative Site 576
🇵🇱Kobierzyce, Poland
Forest Investigative Site 628
🇷🇸Novi Sad, Serbia
Forest Investigative Site 728
🇪🇸Sabadell, Barcelona, Spain
Forest Investigative Site 326
🇫🇷Paris, France
Forest Investigative Site 378
🇭🇺Budapest, Hungary
Forest Investigative Site 062
🇺🇸Orlando, Florida, United States
Forest Investigative Site 061
🇺🇸Louisville, Kentucky, United States
Forest Investigative Site 005
🇺🇸Phoenix, Arizona, United States
Forest Investigative Site 021
🇺🇸San Francisco, California, United States
Forest Investigative Site 125
🇺🇸Orlando, Florida, United States
Forest Investigative Site 114
🇺🇸Orlando, Florida, United States
Forest Investigative Site 084
🇺🇸Indianapolis, Indiana, United States
Forest Investigative Site 118
🇺🇸Miami, Florida, United States
Forest Investigative Site 124
🇺🇸Orlando, Florida, United States
Forest Investigative Site 067
🇺🇸Tampa, Florida, United States
Forest Investigative Site 056
🇺🇸Indianapolis, Indiana, United States
Forest Investigative Site 104
🇺🇸Las Vegas, Nevada, United States
Forest Investigative Site 019
🇺🇸Oklahoma City, Oklahoma, United States
Forest Investigative Site 057
🇺🇸Nashville, Tennessee, United States
Forest Investigative Site 029
🇺🇸Salt Lake City, Utah, United States
Forest Investigative Site 085
🇺🇸Oakland Park, Florida, United States
Forest Investigative Site 227
🇨🇴Barranquilla, Colombia
Forest Investigative Site 380
🇭🇺Szeged, Hungary
Forest Investigative Site 452
🇮🇹Siena, Italy
Forest Investigative Site 097
🇺🇸Lincoln, Nebraska, United States
Forest Investigative Site 701
🇰🇷Seoul, Korea, Republic of
Forest Investigative Site 401
🇮🇸Kopavogur, Iceland
Forest Investigative Site 580
🇵🇱Kielce, Poland
Forest Investigative Site 629
🇷🇸Nis, Serbia
Forest Investigative Site 807
🇺🇦Kharkiv, Ukraine
Forest Investigative Site 801
🇺🇦Odesa, Ukraine
Forest Investigative Site 704
🇰🇷Yangsan-si, Gyeongsangnam-do, Korea, Republic of
Forest Investigative Site 626
🇷🇸Belgrade, Serbia
Forest Investigative Site 627
🇷🇸Belgrade, Serbia
Forest Investigative Site 651
🇸🇬Singapore, Singapore
Forest Investigative Site 730
🇪🇸Torremolinos, Málaga, Spain
Forest Investigative Site 091
🇺🇸New Orleans, Louisiana, United States
Forest Investigative Site 072
🇺🇸Chapel Hill, North Carolina, United States
Forest Investigative Site 105
🇺🇸Charleston, South Carolina, United States
Forest Investigative Site 376
🇭🇺Budapest, Hungary