Autistic DisorderPhase 2NCT01592747
Withdrawal Study of Memantine in Pediatric Patients With Autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified Previously Treated With Memantine
A Phase 2 study testing Memantine Hydrochloride (HCl) in people with Autistic Disorder and Autism, run by Forest Laboratories at 94 sites in 15 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 6 to 12 years
- Conditions the study is for
- Autistic Disorder, Autism, Asperger's Disorder
- What is being tested?
- Memantine Hydrochloride (HCl)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 479 participants
- Where
- 94 sitesin 15 countries
- Study dates
- Sep 2012to Oct 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Completed at least 12 weeks of exposure to study drug in lead-in study MEM-MD-91 (NCT01592786)
- Met responder criterion at two consecutive visits separated by at least two weeks in lead-in study MEM-MD-91
- 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
- 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
- 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
- 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
Show all 9Show fewer
- 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
- Females who are 9 years and older or who have had onset of menses must have a negative urine pregnancy test at Visit 1
- Age of 6 years to 12 years at the time of entry into lead in study MEM-MD-91
Who cannot join
- 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
- 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.
- 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
- 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
- Patients requiring treatment with prohibited concomitant medications
- Patients who, in the opinion of the Investigator, might not be suitable for the study
- Employee or immediate relative of an employee of Forest Laboratories, Inc., any of its affiliates or partners, or the study center
Trial locations and contacts
94 sites in 15 countries.
94 sites in 15 countries
United States64 sites
Forest Investigative Site 081
Albuquerque, New Mexico, 87108-5129
Forest Investigative Site 107
Albuquerque, New Mexico, 87109
Forest Investigative Site 069
Avon Lake, Ohio, 44012
Forest Investigative Site 071
Bothell, Washington, 98011
Forest Investigative Site 078
Boulder, Colorado, 80304
Forest Investigative Site 075
Bradenton, Florida, 32751
Forest Investigative Site 073
Centennial, Colorado, 80112
Forest Investigative Site 072
Chapel Hill, North Carolina, 27514
Forest Investigative Site 105
Charleston, South Carolina, 29407
Forest Investigative Site 119
Charleston, West Virginia, 25304
Forest Investigative Site 064
Charlottesville, Virginia, 22903
Forest Investigative Site 028
Clinton, Utah, 84015
Forest Investigative Site 001
Columbus, Ohio, 43210
Forest Investigative Site 068
Dothan, Alabama, 36303
Forest Investigative Site 082
Evansville, Indiana, 47713
Forest Investigative Site 080
Gainesville, Florida, 32607
Forest Investigative Site 054
Glendale, California, 91206
Forest Investigative Site 053
Gresham, Oregon, 97030
Forest Investigative Site 130
Henderson, Nevada, 89052
Forest Investigative Site 051
Houston, Texas, 77090
Forest Investigative Site 109
Imperial, California, 92251
Forest Investigative Site 056
Indianapolis, Indiana, 46260
Forest Investigative Site 117
Jacksonville, Florida, 32216
Forest Investigative Site 132
Johnstown, Pennsylvania, 15904
Forest Investigative Site 095
Lake Charles, Louisiana, 70605
Forest Investigative Site 104
Las Vegas, Nevada, 89128
Forest Investigative Site 102
Libertyville, Illinois, 60048
Forest Investigative Site 116
Lincoln, Nebraska, 68516
Forest Investigative Site 097
Lincoln, Nebraska, 68526
Forest Investigative Site 077
Little Rock, Arkansas, 72202-3591
Forest Investigative Site 096
Los Angeles, California, 90024
Forest Investigative Site 061
Louisville, Kentucky, 40202
Forest Investigative Site 065
Maitland, Florida, 32751
Forest Investigative Site 131
McMurray, Pennsylvania, 15317
Forest Investigative Site 100
Media, Pennsylvania, 19063
Forest Investigative Site 090
Memphis, Tennessee, 38119
Forest Investigative Site 118
Miami, Florida, 33155
Forest Investigative Site 063
Middleton, Wisconsin, 53562
Forest Investigative Site 023
Naperville, Illinois, 60563
Forest Investigative Site 057
Nashville, Tennessee, 37232
Forest Investigative Site 136
Neptune City, New Jersey, 07753
Forest Investigative Site 059
Newton, Massachusetts, 02459
Forest Investigative Site 113
Norfolk, Virginia, 23507
Forest Investigative Site 085
Oakland Park, Florida, 33334
Forest Investigative Site 141
Ogden, Utah, 84405
Forest Investigative Site 019
Oklahoma City, Oklahoma, 73116
Forest Investigative Site 115
Orange City, Florida, 32763
Forest Investigative Site 125
Orlando, Florida, 32803
Forest Investigative Site 062
Orlando, Florida, 32806
Forest Investigative Site 005
Phoenix, Arizona, 85006
Forest Investigative Site 086
Rockville, Maryland, 20852
Forest Investigative Site 029
Salt Lake City, Utah, 84106
Forest Investigative Site 021
San Francisco, California, 94143-0984
Forest Investigative Site 026
Santa Ana, California, 92701
Forest Investigative Site 108
Springfield, Massachusetts, 01199
Forest Investigative Site 002
Stanford, California, 94305-5719
Forest Investigative Site 067
Tampa, Florida, 33612
Forest Investigative Site 070
The Woodlands, Texas, 77381
Forest Investigative Site 127
Toms River, New Jersey, 08755
Forest Investigative Site 055
Tucson, Arizona, 85718
Forest Investigative Site 092
Tulsa, Oklahoma, 74104
Forest Investigative Site 052
Washington D.C., District of Columbia, 20010-2970
Forest Investigative Site 101
Wellington, Florida, 33414
Forest Investigative Site 106
Wichita, Kansas, 67214-3199
Poland4 sites
Forest Investigative Site 579
Gdansk, 80-542
Forest Investigative Site 578
Gdansk, 80-952
Forest Investigative Site 576
Kobierzyce, 55-040
Forest Investigative Site 577
Warsaw, 02-957
Serbia4 sites
Forest Investigative Site 626
Belgrade, 11000
Forest Investigative Site 627
Belgrade, 11000
Forest Investigative Site 629
Niš, 18000
Forest Investigative Site 628
Novi Sad, 21000
South Korea4 sites
Forest Investigative Site 702
Seoul, 110744
Forest Investigative Site 703
Seoul, 120-752
Forest Investigative Site 701
Seoul, 138-736
Forest Investigative Site 704
Yangsan, Gyeongsangnam-do, 626-770
Hungary3 sites
Forest Investigative Site 381
Budapest, 1026
Forest Investigative Site 376
Budapest, 1083
Forest Investigative Site 378
Budapest, 1089
Ukraine3 sites
Forest Investigative Site 807
Kharkiv, 61153
Forest Investigative Site 802
Kherson,Vil. Stepanivka, 73488
Forest Investigative Site 804
Kyiv, 04080
Belgium2 sites
Forest Investigative Site 204
Brussels, 1020
Forest Investigative Site 203
Brussels, 1090
Colombia2 sites
Forest Investigative Site 228
Bello
Forest Investigative Site 226
Bogotá
Italy2 sites
Forest Investigative Site 453
Roma, 165
Forest Investigative Site 452
Siena, 53100
South Africa1 site
Forest Investigative Site 676
Cape Town, Western Cape, 7530
About this study
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
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).
Read the 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)
- Being tested
- Memantine Hydrochloride (HCl), Placebo capsules
- Keywords
- Asperger's, Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS), Memantine, Pediatric Disorder, Randomized Controlled Trial
- Medical subject headings
- Autistic Disorder, Asperger Syndrome, Autism Spectrum Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Memantine Hydrochloride (HCl)Drug
Extended Release Dose ranging from 3-15mg/day; administered orally
Memantine Hydrochloride (HCl)Drug
Extended Release Dose ranging from 3mg every other day to 6mg/day; administered orally.
Placebo capsulesDrug
Once daily, oral administration.
| Study group | Role | What they receive |
|---|---|---|
| Memantine 1 | Experimental | 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. Receives: Drug: Memantine Hydrochloride (HCl) |
| Memantine 2 | Experimental | 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. Receives: Drug: Memantine Hydrochloride (HCl) |
| Placebo | Placebo comparator | Dosing will be once daily for up to 12 weeks. Receives: Drug: Placebo capsules |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Patients Meeting the Criterion for Loss of Therapeutic Response (LTR) by the End of the Study (Based on Observed Cases)
Loss of Therapeutic response is defined as a worsening (increase) of at least 10 points in Social Responsiveness Scale (SRS) total raw score relative to the Visit 1 (randomization) score. The Social Responsiveness Scale (SRS) is a 65-item informant-rated assessment with total raw score ranging from 0 (no impairment) to 195 (severe social impairment). Each item is associated with 1 of 5 subscales (social awareness, social cognition, social communication, social motivation and autistic mannerisms). Each item is rated on a 4-point scale from 1 (not true) to 4 (almost always true). The scores are then transposed to a scale from 0 to 3 and scores are summed within each of the 5 subscales. A higher score indicates greater severity of social impairment.
Measured: Baseline (Visit 1) to week 12
Secondary outcomes (11)
Time to First Loss of Therapeutic (LTR) Response
Time to the first visit when a patient shows LTR following randomization to memantine or placebo.
Measured: Baseline to week 12
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Speech Subscale at Week 12
The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties (items 1-50) and strengths (items 51-70) in communication. There are 10 sub-scales consisting of 7 items each. The Children's Communication Checklist-2 (CCC-2) Speech Subscale consists of 7 items rated from 0 (less than once a week or never) to 3 (several times [more than twice] a day or always), with a total raw score of 0 (mildest) to 21 (most severe).
Measured: Baseline (Visit 1) to week 12
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Syntax Subscale at Week 12
The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties (items 1-50) and strengths (items 51-70) in communication. There are 10 sub-scales consisting of 7 items each. The Children's Communication Checklist-2 (CCC-2) Syntax Subscale consists of 7 items rated from 0 (less than once a week or never) to 3 (several times [more than twice] a day or always), with a total raw score of 0 (mildest) to 21 (most severe).
Measured: Baseline (Visit 1) to week 12
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Semantics Subscale at Week 12
The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties (items 1-50) and strengths (items 51-70) in communication. There are 10 sub-scales consisting of 7 items each. The Children's Communication Checklist-2 (CCC-2) Semantics Subscale consists of 7 items rated from 0 (less than once a week or never) to 3 (several times [more than twice] a day or always), with a total raw score of 0 (mildest) to 21 (most severe).
Measured: Baseline (Visit 1) to week 12
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Coherence Subscale at Week 12
The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties (items 1-50) and strengths (items 51-70) in communication. There are 10 sub-scales consisting of 7 items each. The Children's Communication Checklist-2 (CCC-2) Coherence Subscale consists of 7 items rated from 0 (less than once a week or never) to 3 (several times [more than twice] a day or always), with a total raw score of 0 (mildest) to 21 (most severe).
Measured: Baseline (Visit 1) to week 12
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Initiation Subscale at Week 12
The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties (items 1-50) and strengths (items 51-70) in communication. There are 10 sub-scales consisting of 7 items each. The Children's Communication Checklist-2 (CCC-2) Initiation Subscale consists of 7 items rated from 0 (less than once a week or never) to 3 (several times [more than twice] a day or always), with a total raw score of 0 (mildest) to 21 (most severe).
Measured: Baseline (Visit 1) to week 12
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Scripted Language Subscale at Week 12
The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties (items 1-50) and strengths (items 51-70) in communication. There are 10 sub-scales consisting of 7 items each. The Children's Communication Checklist-2 (CCC-2) Scripted language Subscale consists of 7 items rated from 0 (less than once a week or never) to 3 (several times [more than twice] a day or always), with a total raw score of 0 (mildest) to 21 (most severe).
Measured: Baseline (Visit 1) to week 12
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Context Subscale at Week 12
The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties (items 1-50) and strengths (items 51-70) in communication. There are 10 sub-scales consisting of 7 items each. The Children's Communication Checklist-2 (CCC-2) Context Subscale consists of 7 items rated from 0 (less than once a week or never) to 3 (several times [more than twice] a day or always), with a total raw score of 0 (mildest) to 21 (most severe).
Measured: Baseline (Visit 1) to week 12
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Nonverbal Communication Subscale at Week 12
The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties (items 1-50) and strengths (items 51-70) in communication. There are 10 sub-scales consisting of 7 items each. The Children's Communication Checklist-2 (CCC-2) Nonverbal communication Subscale consists of 7 items rated from 0 (less than once a week or never) to 3 (several times [more than twice] a day or always), with a total raw score of 0 (mildest) to 21 (most severe).
Measured: Baseline (Visit 1) to week 12
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Social Relations Subscale at Week 12
The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties (items 1-50) and strengths (items 51-70) in communication. There are 10 sub-scales consisting of 7 items each. The Children's Communication Checklist-2 (CCC-2) Social Relations Subscale consists of 7 items rated from 0 (less than once a week or never) to 3 (several times [more than twice] a day or always), with a total raw score of 0 (mildest) to 21 (most severe).
Measured: Baseline (Visit 1) to week 12
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Interests Subscale at Week 12
The Children's Communication Checklist-2 (CCC-2) is a validated, norm-referenced, informant-rated scale that evaluates difficulties (items 1-50) and strengths (items 51-70) in communication. There are 10 sub-scales consisting of 7 items each. The Children's Communication Checklist-2 (CCC-2) Interests Subscale consists of 7 items rated from 0 (less than once a week or never) to 3 (several times [more than twice] a day or always), with a total raw score of 0 (mildest) to 21 (most severe).
Measured: Baseline (Visit 1) to week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2012 (estimated)
- Study startSep 2012
- Primary completionSep 2013
- Study completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Autistic DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 479 participants (actual)
Sponsor and investigators
- Lead sponsor
- Forest Laboratories
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jordan Lateiner, MS, MBA, Study director, Forest Research Institute, Inc.- A Subsidiary of Forest Laboratories, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01592747
- Sponsor's protocol ID
- MEM-MD-68
- Status last verified
- Mar 2019
- First submitted
- 3 May 2012
- Last updated
- 24 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 37811711Brignell 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.
PubMed 36006807
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01592747
- Acronym / sponsor ID
- MEM-MD-68
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 479 participants (actual)
- Lead sponsor
- Forest LaboratoriesIndustry (pharma, biotech, devices)
- Study start
- Sep 2012
- Primary completion
- Sep 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 7 May 2012 (estimated)
- Results
- Posted 24 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Memantine 1 | Experimental | Drug: Memantine Hydrochloride (HCl)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. |
| Memantine 2 | Experimental | Drug: Memantine Hydrochloride (HCl)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. |
| Placebo | Placebo comparator | Drug: Placebo capsulesDosing will be once daily for up to 12 weeks. |
Who may qualify
- Ages
- 6 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- Completed at least 12 weeks of exposure to study drug in lead-in study MEM-MD-91 (NCT01592786)
- Met responder criterion at two consecutive visits separated by at least two weeks in lead-in study MEM-MD-91
- 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
- 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
- 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
Key exclusion criteria (7 listed)
- 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
- 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.
- 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
- 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
- Patients requiring treatment with prohibited concomitant medications
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Memantine Hydrochloride (HCl)Extended Release Dose ranging from 3-15mg/day; administered orally | Drug | Memantine 1 |
| Memantine Hydrochloride (HCl)Extended Release Dose ranging from 3mg every other day to 6mg/day; administered orally. | Drug | Memantine 2 |
| Placebo capsulesOnce daily, oral administration. | Drug | Placebo |
Primary outcome
Proportion of Patients Meeting the Criterion for Loss of Therapeutic Response (LTR) by the End of the Study (Based on Observed Cases)
Time frame: Baseline (Visit 1) to week 12
Loss of Therapeutic response is defined as a worsening (increase) of at least 10 points in Social Responsiveness Scale (SRS) total raw score relative to the Visit 1 (randomization) score. The Social Responsiveness Scale (SRS) is a 65-item informant-rated assessment with total raw score ranging from 0 (no impairment) to 195 (severe social impairment). Each item is associated with 1 of 5 subscales (social awareness, social cognition, social communication, social motivation and autistic mannerisms). Each item is rated on a 4-point scale from 1 (not true) to 4 (almost always true). The scores are then transposed to a scale from 0 to 3 and scores are summed within each of the 5 subscales. A higher score indicates greater severity of social impairment.
11 secondary outcomes
Time to First Loss of Therapeutic (LTR) Response
Time frame: Baseline to week 12
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Speech Subscale at Week 12
Time frame: Baseline (Visit 1) to week 12
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Syntax Subscale at Week 12
Time frame: Baseline (Visit 1) to week 12
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Semantics Subscale at Week 12
Time frame: Baseline (Visit 1) to week 12
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Coherence Subscale at Week 12
Time frame: Baseline (Visit 1) to week 12
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Initiation Subscale at Week 12
Time frame: Baseline (Visit 1) to week 12
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Scripted Language Subscale at Week 12
Time frame: Baseline (Visit 1) to week 12
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Context Subscale at Week 12
Time frame: Baseline (Visit 1) to week 12
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Nonverbal Communication Subscale at Week 12
Time frame: Baseline (Visit 1) to week 12
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Social Relations Subscale at Week 12
Time frame: Baseline (Visit 1) to week 12
Change From Baseline in Children's Communication Checklist-2 (CCC-2) - Interests Subscale at Week 12
Time frame: Baseline (Visit 1) to week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37811711Iffland 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.
- Derived from this study: PubMed 36006807Brignell 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jordan Lateiner, MS, MBA study director
Forest Research Institute, Inc.- A Subsidiary of Forest Laboratories, Inc.
94 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Memantine Hydrochloride (HCl) in people with Autistic Disorder and Autism, run by Forest Laboratories at 94 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 94 sites in United States, Poland, Serbia, South Korea, Hungary and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Patients Meeting the Criterion for Loss of Therapeutic Response (LTR) by the End of the Study (Based on Observed Cases) (time frame: Baseline (Visit 1) to week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01592747, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2019.