Antonio Hardan
Study of Pharmacokinetics, Safety, Efficacy, and Tolerability of Memantine in Children With Autism
Contact Information
Stanford University School of Medicine 300 Pasteur Drive Stanford, CA 94305Brief
The purpose of this study is to investigate the pharmacokinetics, safety, tolerability, and efficacy of memantine in pediatric patients with autism. We hope to learn whether or not the drug memantine can beneficially effect some of the core symptoms of autism, including social responsivness and communication skills.
Recruiting Status:
RecruitingStanford Recruiting Status:
RecruitingCondition(s):
Intervention(s):
- Drug: Memantine
Phase:
Phase 2Eligibility
Ages Eligible for Study:
6 years to 12 yearsGenders Eligible for Study:
Male and FemaleHealth of Volunteers:
People with the conditions listed in this trial can participate as controls.Key Inclusion Criteria:
Inclusion Criteria:
Patients must fulfill all of the following criteria to be considered for inclusion into
Part One of this study at Screening (Visit 1.1):
1. Written informed assent obtained from the patient, when developmentally
appropriate, before the initiation of any study-specific procedures. Written informed
consent for the patient??s participation must be obtained from the parent, legal
guardian, or LAR
2. Male or premenarcheal female outpatients
3. Age of 6 to 12 years
4. Diagnosis of autistic disorder, Asperger disorder, or PDD not otherwise specified
according to DSM-IV-TR criteria using any of the validated diagnostic scales listed
below:
?? ADI-R
?? Autism Diagnostic Observation Schedule (ADOS)?CSocial Interaction and
Communication subscale
?? Childhood Autism Rating Scale
?? Gilliam Autism Rating Scale
?? Gilliam Asperger Scale
?? Social Communication Questionnaire
5. Normal physical examination and laboratory test results at Screening (Visit 1.1). Any abnormal findings must be deemed not clinically significant by the Investigator and documented
6. Females who are 9 years and older must have a negative serum pregnancy test at screening and a negative urine pregnancy test at Visits PK1, 2, 3, 4, 5, 6, and 7. The parent, legal guardian, or LAR must provide consent, and the patient must provide assent, for these procedures
7. Normal sitting pulse rate. Patients aged 6 to 10 years inclusive must have a pulse rate not greater than 133 bpm or not less than 65 bpm by vital sign assessment. Patients aged 11 to 12 years inclusive must have a pulse rate not greater than 119 bpm or not less than 60 bpm by vital sign assessment
8. Normal sitting BP. Patients aged 6 to 10 years inclusive must have a sitting systolic BP no greater than 121 mm Hg and no less than 75 mm Hg and a sitting diastolic BP no greater than 78 mm Hg and no less than 35 mm Hg at Screening (Visit 1.1).
Patients aged 11 to 12 years inclusive must have a sitting systolic BP no greater than
134 mm Hg and no less than 87 mm Hg and a sitting diastolic BP no greater than
82 mm Hg and no less than 44 mm Hg at Screening (Visit 1.1)
9. 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 study drug
10. The patient, parent or LAR, and caregiver must be able to speak and understand English sufficiently to understand the nature of the study and to allow for the completion of all study assessments
11. Ability to tolerate venipuncture procedures for blood sampling
The following additional inclusion criteria for Part Two must be met for patients who participate Part Two only at Screening (Visit 1.2) and Visit 2 (Baseline) and patients who have completed Part One before randomization at Visit 2 (Baseline):
12. Meet DSM-IV-TR diagnostic criteria for autism based on:
?? Autism Diagnostic Observation Schedule?CSocial Interaction and Communication Modules 2 or 3
?? ADI-R
13. English is the language the child speaks most frequently and is most comfortable using
14. Verbally fluent (at least three-word phrases). Must use some phrase speech if not verbally fluent
15. An ABC irritability subscale score <17
16. An SRS raw total score > 44 for females and > 53 for males
17. 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,
at Visit 2 (Baseline)
18. If the patient is already receiving stable nonpharmacologic, dietary, educational,
and/or behavioral interventions, participation in these programs must have been
continuous during the 90 days before Screening (Visit 1.1 or Visit 1.2) and the family
must intend to maintain the treatment/intervention for the duration of the current
study. All patients or their caregiver/legal guardian/LAR will agree not to initiate new
or modify ongoing interventions for the duration of the study
Patients who complete Part One or Study MEM-PK-21 will be eligible for enrollment into Part Two even if they do not fulfill all of the inclusion criteria.
Key Exclusion Criteria:
Exclusion Criteria:
Patients who fulfill one or more of the following criteria at Screening (Visit 1.1 or Visit 1.2) will be excluded from this study:
1. History of premature birth (before 35 weeks gestational age or weight of < 5 lb at birth)
2. History of hypersensitivity reaction to memantine, dextromethorphan,
amantadine, or any other NMDA receptor antagonists
3. Medical history of neurological disease including, but not limited to, active epilepsy/seizure disorder (defined as seizure activity within 5 years of screening [Visit 1.1 or Visit 1.2]) except simple febrile seizures, movement disorder, or Tourette syndrome, tuberous sclerosis, fragile X syndrome or any other known genetic syndromes; known abnormal computed tomography/magnetic resonance
imaging of the brain; or a structural lesion of the brain
4. 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
5. Clinically significant ECG abnormalities such as: a PR interval of greater than or
equal to 170 msec for patients aged 5 to under 11 years and greater than or equal to 200 msec for patients aged 11 to 12 years inclusive; QT prolongation
(QTc ?? 440 msec for patients aged 5 to under 11 years and ?? 425 msec for patients aged 11 to 12 years inclusive using the Bazett correction); sinus bradycardia (< 65 bpm for patients aged 5 to under 11 years and < 60 bpm for patients aged 11 to 12 years inclusive); sick sinus syndrome; first-, second-, or third-degree atrioventricular block; any type of tachycardia; more than one PVC on a 12-lead ECG; complete left bundle branch block; nonsinus rhythm; or evidence of myocardial
ischemia/infarction (either changes suggesting acute ischemia/infarction or changes from previous tracings compatible with the infarction during the preceding 6 months)
6. 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
7. Taking excluded concomitant medications listed in Appendix II
8. Treatment with memantine or participation in an investigational study of memantine within 90 days of Screening (Visit 1.1 or Visit 1.2), with the exception of Study MEM-PK-21
9. Patients who, in the Investigator??s and/or Sponsor??s opinion, might not be suitable for the study All diagnostic information (eg, diagnostic scales used, medical history) should be
documented in the source documents and should lead to a diagnosis of ASD (Autism, Asperger syndrome, and PDD-NOS). Any exceptions to the inclusion/exclusion criteria will be considered on a case-by-case
basis and will be documented in the source documents and eCRF. All exceptions need Sponsor approval before the patient is enrolled in the study. For the physical examination, laboratory evaluations, vital sign assessments, and ECG results, any
abnormal findings must be judged not clinically significant by the Investigator and documented as such in the source documents and eCRF.
All the exclusion criteria for Visit 1.1 will also apply to Visit 1.2. The following
additional exclusion criteria for Part Two will apply for patients who participate in
Part Two only at Screening (Visit 1.2) and Visit 2 (Baseline) and patients who have completed Part One before randomization at Visit 2 (Baseline):
10. Having any primary psychiatric (Axis I) diagnosis other than autism
11. 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
12. Taking, or having taken psychoactive medications (eg, stimulants, antidepressants,
antipsychotics, antiepileptics, anxiolytics, clonidine) or any other excluded
concomitant medications (Appendix II) within five half-lives or 4 weeks of Screening (Visit 1.1 or Visit 1.2), whichever is shorter. For patients treated with fluoxetine, the minimum washout duration will be 6 weeks before Screening (Visit 1.1 or Visit 1.2) Patients who complete Part One or Study MEM-PK-21 will be eligible for enrollment to Part Two even if they meet any or all exclusion criteria.
Additional Study Details
Official Title:
An Open-label (Part One) and a Randomized, Double-blind, Placebo-Controlled(Part Two) Study of the Pharmacokinetics, Safety, Efficacy, and Tolerability of Memantine in Pediatric Patients With AutismAnticipated start date:
9/2/2009Lead Sponsor:
Forest LaboratoriesInvestigator(s):
Study Type:
InterventionalPurpose:
TreatmentAllocation:
RandomizedMasking:
Double BlindControl:
noneAssignment:
ParallelEndpoints:
Safety/EfficacyPrimary Outcomes:
- Change in Social Responsiveness Scale
Secondary Outcomes:
- Change in Core Autism Treatment Scale-Improvement
- Change in Children's Communication Checklist
Total Number to be Enrolled:
104Total Number to be Enrolled at Stanford:
6More Information
Secondary ID(s):
- MEM-MD-57A
- NCT00872898
- eProtocol 15648
Locations & Contacts
Stanford Locations & Contacts:
Stanford University School of Medicine 300 Pasteur Drive Stanford, CA 94305Non-Stanford Locations:
The Stanford website does not have any locations outside of Stanford listed for this trial. You may want to check clinicaltrials.gov for posible additional locations.
This listing was last updated:
9/20/2009PLEASE NOTE:
Study Coordinators and Research Nurses cannot give medical advice over the phone. Telephone numbers are provided for obtaining additional information on specific clinical research trials only. If you have specific questions which require clinical expertise, please call your primary care physician. If you do not have a primary care physician please feel free to call the SHC Physician Referral Service at (800) 756-9000 or send an email.
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