Autism or Asperger’s Disorder or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) MedDRA version: 14.1 Level: PT Classification code 10003484 Term: Asperger's disorder System Organ Class: 10037175 - Psychiatric disorders MedDRA version: 14.1 Level: LLT Classification code 10008520 Term: Childhood autism System Organ Class: 10029205 - Nervous system disorders MedDRA version: 14.1 Level: LLT Classification code 10034739 Term: Pervasive developmental disorder NOS System Organ C
Conditions
Interventions
Product Name: Memantine Hydrochloride
Product Code: MRZ 2/145
Pharmaceutical Form: Prolonged-release capsule
INN or Proposed INN: MEMANTINE HYDROCHLORIDE
CAS Number: 41100-52-1
Concentration unit: mg
Sponsors
Forest Research Institute, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible to participate in the study, patients must meet the following criteria: 1. 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. 2. Male or female outpatients 3. Age of 6-12 4. Females who are 9 years and older or who have had onset of menses must have a negative serum pregnancy test at screening 5. Meet DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) diagnostic criteria for autism, Asperger’s Disorder, or PDD-NOS based on both: ? ADOS (Autism Diagnostic Observation Schedule) Modules 2 or 3 ? ADI-R (Autism Diagnostic Interview–Revised) ADOS completed within the 6 months before Screening and ADI-R completed within the 3 months before Screening are acceptable provided that the assessments were done by a qualified rater. A copy of the scores must be available for the source file and the eCRF. 6. Normal physical examination and laboratory test results at Screening (Visit 0) or any abnormal findings must be deemed not clinically significant by the Investigator and documented 7. Normal sitting pulse rate by vital sign assessment. Any deviation from normal must be judged not clinically significant by the Investigator. Please refer to Appendix V for Normal ranges 8. Normal sitting blood pressure (BP). Any deviation from normal must be judged not clinically significant by the Investigator. 9. Ability to tolerate venipuncture procedures for blood sampling 10. A knowledgeable caregiver capable of providing reliable information about the patient’s condition, able to attend all clinic visits with the patient, and able to oversee the administration of investigational product. Every effort should be made to maintain the same caregiver throughout the study 11. 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 12. 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 13. Verbally fluent (at least three-word phrases). Must use some phrase speech if not verbally fluent 14. An SRS (Social Responsiveness Scale) total raw score > 44 for females and > 53 for males 15. An IQ in the not mentally retarded or mildly retarded range as measured by a standardized score of 50 or higher on the Kaufman Brief Intelligence Test, Version 2, or by other standard IQ test used for non-English speakers and in the countries outside the United States and Canada where the study is being conducted, at Screening (Visit 0) Are the trial subjects under 18? yes Number of subjects for this age range: 192 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria will not be eligible to participate in the study: 1. Have enrolled in Study MEM-MD-57A 2. History of premature birth (before 35 weeks gestational age or weight of < 5 lb at birth) 3. History of hypersensitivity reaction to memantine, dextromethorphan, amantadine, or any other NMDA receptor antagonists 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 6. An ABC (Aberrant Behavior Checklist) Irritability subscale (ABC-I) score = 17 at Screening (Visit 0) 7. Significant risk of suicidality based on the investigator judgment, ABC-I, or if appropriate, as indicated by a response of “yes” to questions 3, 4, or 5 in the suicidal ideation section of the Children’s Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening (Visit 0) or any suicidal behavior within the past 6 months. 8. Taking, or having taken NMDA antagonists (eg, amantadine, ketamine, dextromethorphan) or any other excluded concomitant medications (Appendix III) within five half-lives or 4 weeks of Screening (Visit 0), whichever is shorter. 9. Medical history of neurological disease including, but not limited to, movement disorder; Tourette syndrome; tuberous sclerosis; fragile X syndrome; velocardiofacial syndrome; chromosome 15q duplication syndrome; Angelman syndrome; active epilepsy/seizure disorder (defined as seizure activity within 5 years of screening (Visit 0) except simple febrile seizures; known abnormal computed tomography/magnetic resonance imaging of the brain; or a structural lesion of the brain 10. Medical conditions that might interfere with the conduct of the study, confound interpretation of the study results, or endanger the patient’s well-being. Such conditions include, but are not limited to, evidence or history of malignancy or any significant hematologic, endocrine, cardiovascular (including any rhythm disorder), respiratory, renal, hepatic, or gastrointestinal disease. If there is a history of such disease but the condition has been stable for more than 1 year and is judged by the Investigator not to interfere with the patient’s participation in the study, the patient may be included, with the documented approval of the Study Physician 11. Clinically significant ECG abnormalities. Any deviation from normal must be judged not clinically significant by the Investigator. Please refer to Appendix V for out of normal ranges ECG values and findings 12. Participation in any other clinical investigation using an experimental drug or requiring repeated blood draws within 30 days of the start of this study or participation in a blood donation program within the past 60 days 13. Treatment with memantine or participation in an investigational study of memantine within 90 days of Screening (Visit 0) 14. 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 15. Patients who, in the Investigator’s and/or Sponsor’s opinion, might not be suitable for te study 16. Employee or immediate relative of an employee of Forest Laboratories, Inc., any of its affiliates or partners, or the study center
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective 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 the follow-up randomized withdrawal study;Secondary Objective: not applicable;Primary end point(s): 1) Complete at least 12 weeks of exposure to investigational product and 2) Meet the responder criterion at two consecutive visits separated by at least two weeks. A patient will be considered a responder if he or she presented at least 10 points improvement (reduction in score) in SRS relative to the Visit 1 total raw score.;Timepoint(s) of evaluation of this end point: Patients meeting the confirmed responder criteria any time at or after Visit 5 (end of Week 12) will be expected to transition to a follow-up randomized withdrawal study (MEM-MD-68). SRS will be administered at Visits 0, 1, 4A, 5, 5A, 6, 6A, 7, 7A, 8, and confirmatory visits. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): No secondary objectives;Timepoint(s) of evaluation of this end point: Not applicable as no secondary objectives | — |
Countries
Australia, Belgium, Colombia, Denmark, Estonia, Finland, France, Germany, Hungary, Iceland, Ireland, Italy, Korea, Republic of, Mexico, Netherlands, New Zealand, Norway, Philippines, Poland, Russian Federation, Serbia, Singapore, South Africa, Spain, Sweden, Taiwan, Thailand, Ukraine, United Kingdom
Contacts
Public ContactClinical Trial Information Desk
Quintiles Contact Center
Outcome results
None listed