Clinical trial NCT01592747: Withdrawal Study of Memantine in Pediatric Patients With Autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified Previously Treated With Memantine
Official title: A Double-Blind, Placebo-Controlled, Randomized Withdrawal Study of the Safety and Efficacy of Memantine in Pediatric Patients With Autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) Previously Treated With Memantine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Autistic Disorder
Autism
Asperger's Disorder
Asperger Syndrome
Autism Spectrum Disorders
Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS)
Keywords: Asperger's
Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS)
Memantine
Pediatric Disorder
Randomized Controlled Trial
Lead sponsor: Forest Laboratories
Sponsor class: INDUSTRY
First posted: 2012-05-07
Enrollment: 479
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Proportion of Patients Meeting the Criterion for Loss of Therapeutic Response (LTR) by the End of the Study (Based on Observed Cases)
timeFrame: Baseline (Visit 1) to week 12
Secondary outcomes:
measure: Time to First Loss of Therapeutic (LTR) Response
timeFrame: Baseline to week 12
measure: Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Speech Subscale at Week 12
timeFrame: Baseline (Visit 1) to week 12
measure: Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Syntax Subscale at Week 12
timeFrame: Baseline (Visit 1) to week 12
measure: Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Semantics Subscale at Week 12
timeFrame: Baseline (Visit 1) to week 12
measure: Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Coherence Subscale at Week 12
timeFrame: Baseline (Visit 1) to week 12
measure: Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Initiation Subscale at Week 12
timeFrame: Baseline (Visit 1) to week 12
measure: Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Scripted Language Subscale at Week 12
timeFrame: Baseline (Visit 1) to week 12
measure: Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Context Subscale at Week 12
timeFrame: Baseline (Visit 1) to week 12
measure: Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Nonverbal Communication Subscale at Week 12
timeFrame: Baseline (Visit 1) to week 12
measure: Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Social Relations Subscale at Week 12
timeFrame: Baseline (Visit 1) to week 12
measure: Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Interests Subscale at Week 12
timeFrame: Baseline (Visit 1) to week 12
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Forest Investigative Site 068
state: Alabama
city: Phoenix
country: United States
facility: Forest Investigative Site 005
state: Arizona
city: Tucson
country: United States
facility: Forest Investigative Site 055
state: Arizona
city: Little Rock
country: United States
facility: Forest Investigative Site 077
state: Arkansas
city: Glendale
country: United States
facility: Forest Investigative Site 054
state: California
city: Imperial
country: United States
facility: Forest Investigative Site 109
state: California
city: Los Angeles
country: United States
facility: Forest Investigative Site 096
state: California
city: San Francisco
country: United States
facility: Forest Investigative Site 021
state: California
city: Santa Ana
country: United States
facility: Forest Investigative Site 026
state: California
city: Stanford
country: United States
facility: Forest Investigative Site 002
state: California
city: Boulder
country: United States
facility: Forest Investigative Site 078
state: Colorado
city: Centennial
country: United States
facility: Forest Investigative Site 073
state: Colorado
city: Washington
country: United States
facility: Forest Investigative Site 052
state: District of Columbia
city: Bradenton
country: United States
facility: Forest Investigative Site 075
state: Florida
city: Gainesville
country: United States
facility: Forest Investigative Site 080
state: Florida
city: Jacksonville
country: United States
facility: Forest Investigative Site 117
state: Florida
city: Maitland
country: United States
facility: Forest Investigative Site 065
state: Florida
city: Miami
country: United States
facility: Forest Investigative Site 118
state: Florida
city: Oakland Park
country: United States
facility: Forest Investigative Site 085
state: Florida
city: Orange City
country: United States
facility: Forest Investigative Site 115
state: Florida
city: Orlando
country: United States
facility: Forest Investigative Site 125
state: Florida
city: Orlando
country: United States
facility: Forest Investigative Site 062
state: Florida
city: Tampa
country: United States
facility: Forest Investigative Site 067
state: Florida
city: Wellington
country: United States
facility: Forest Investigative Site 101
state: Florida
city: Libertyville
country: United States
facility: Forest Investigative Site 102
state: Illinois
city: Naperville
country: United States
facility: Forest Investigative Site 023
state: Illinois
city: Evansville
country: United States
facility: Forest Investigative Site 082
state: Indiana
city: Indianapolis
country: United States
facility: Forest Investigative Site 056
state: Indiana
city: Wichita
country: United States
facility: Forest Investigative Site 106
state: Kansas
city: Louisville
country: United States
facility: Forest Investigative Site 061
state: Kentucky
city: Lake Charles
country: United States
facility: Forest Investigative Site 095
state: Louisiana
city: Rockville
country: United States
facility: Forest Investigative Site 086
state: Maryland
city: Newton
country: United States
facility: Forest Investigative Site 059
state: Massachusetts
city: Springfield
country: United States
facility: Forest Investigative Site 108
state: Massachusetts
city: Lincoln
country: United States
facility: Forest Investigative Site 116
state: Nebraska
city: Lincoln
country: United States
facility: Forest Investigative Site 097
state: Nebraska
city: Henderson
country: United States
facility: Forest Investigative Site 130
state: Nevada
city: Las Vegas
country: United States
facility: Forest Investigative Site 104
state: Nevada
city: Neptune
country: United States
facility: Forest Investigative Site 136
state: New Jersey
city: Toms River
country: United States
facility: Forest Investigative Site 127
state: New Jersey
city: Albuquerque
country: United States
facility: Forest Investigative Site 081
state: New Mexico
city: Albuquerque
country: United States
facility: Forest Investigative Site 107
state: New Mexico
city: Chapel Hill
country: United States
facility: Forest Investigative Site 072
state: North Carolina
city: Avon Lake
country: United States
facility: Forest Investigative Site 069
state: Ohio
city: Columbus
country: United States
facility: Forest Investigative Site 001
state: Ohio
city: Oklahoma City
country: United States
facility: Forest Investigative Site 019
state: Oklahoma
city: Tulsa
country: United States
facility: Forest Investigative Site 092
state: Oklahoma
city: Gresham
country: United States
facility: Forest Investigative Site 053
state: Oregon
city: Johnstown
country: United States
facility: Forest Investigative Site 132
state: Pennsylvania
city: McMurray
country: United States
facility: Forest Investigative Site 131
state: Pennsylvania
city: Media
country: United States
facility: Forest Investigative Site 100
state: Pennsylvania
city: Charleston
country: United States
facility: Forest Investigative Site 105
state: South Carolina
city: Memphis
country: United States
facility: Forest Investigative Site 090
state: Tennessee
city: Nashville
country: United States
facility: Forest Investigative Site 057
state: Tennessee
city: Houston
country: United States
facility: Forest Investigative Site 051
state: Texas
city: The Woodlands
country: United States
facility: Forest Investigative Site 070
state: Texas
city: Clinton
country: United States
facility: Forest Investigative Site 028
state: Utah
city: Ogden
country: United States
facility: Forest Investigative Site 141
state: Utah
city: Salt Lake City
country: United States
facility: Forest Investigative Site 029
state: Utah
city: Charlottesville
country: United States
facility: Forest Investigative Site 064
state: Virginia
city: Norfolk
country: United States
facility: Forest Investigative Site 113
state: Virginia
city: Bothell
country: United States
facility: Forest Investigative Site 071
state: Washington
city: Charleston
country: United States
facility: Forest Investigative Site 119
state: West Virginia
city: Middleton
country: United States
facility: Forest Investigative Site 063
state: Wisconsin
city: Brussel
country: Belgium
facility: Forest Investigative Site 204
city: Bruxelles
country: Belgium
facility: Forest Investigative Site 203
city: Bello
country: Colombia
facility: Forest Investigative Site 228
city: Bogotá
country: Colombia
facility: Forest Investigative Site 226
city: Tallinn
country: Estonia
facility: Forest Investigative Site 276
city: Bron Cedex
country: France
facility: Forest Investigative Site 329
city: Budapest
country: Hungary
facility: Forest Investigative Site 381
city: Budapest
country: Hungary
facility: Forest Investigative Site 376
city: Budapest
country: Hungary
facility: Forest Investigative Site 378
city: Kopavogur
country: Iceland
facility: Forest Investigative Site 401
city: Roma
country: Italy
facility: Forest Investigative Site 453
city: Siena
country: Italy
facility: Forest Investigative Site 452
city: Yangsan-si
country: Korea, Republic of
facility: Forest Investigative Site 704
state: Gyeongsangnam-do
city: Seoul
country: Korea, Republic of
facility: Forest Investigative Site 702
city: Seoul
country: Korea, Republic of
facility: Forest Investigative Site 703
city: Seoul
country: Korea, Republic of
facility: Forest Investigative Site 701
city: Wellington
country: New Zealand
facility: Forest Investigative Site 526
city: Gdansk
country: Poland
facility: Forest Investigative Site 579
city: Gdansk
country: Poland
facility: Forest Investigative Site 578
city: Kobierzyce
country: Poland
facility: Forest Investigative Site 576
city: Warszawa
country: Poland
facility: Forest Investigative Site 577
city: Belgrade
country: Serbia
facility: Forest Investigative Site 626
city: Belgrade
country: Serbia
facility: Forest Investigative Site 627
city: Nis
country: Serbia
facility: Forest Investigative Site 629
city: Novi Sad
country: Serbia
facility: Forest Investigative Site 628
city: Cape Town
country: South Africa
facility: Forest Investigative Site 676
state: Western Cape
city: Sabadell
country: Spain
facility: Forest Investigative Site 728
state: Barcelona
city: Kharkiv
country: Ukraine
facility: Forest Investigative Site 807
city: Kherson,Vil. Stepanivka
country: Ukraine
facility: Forest Investigative Site 802
city: Kyiv
country: Ukraine
facility: Forest Investigative Site 804
Study officials:
affiliation: Forest Research Institute, Inc.- A Subsidiary of Forest Laboratories, Inc.
name: Jordan Lateiner, MS, MBA
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.