Asperger's, Asperger's Disorder, Autism, Autism Spectrum Disorder (ASD), Autistic Disorder, Pediatric Autism, Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS)
Conditions
Keywords
Autistic Disorder, Asperger's Disorder, Asperger's, Pediatric Autism, Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS), Pervasive Child Development Disorder
Brief summary
The objective of this study is to evaluate the long-term safety and tolerability of memantine in the treatment of pediatric patients with autism, Asperger's Disorder or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS).
Detailed description
This clinical study was a 48-week, multicenter, multinational, open-label extension study in pediatric outpatients with autism, Asperger's Disorder, or PDD-NOS conducted at 106 study centers. Patients were eligible for this long-term extension study if they had: * completed the open-label Study MEM MD 67,or * completed the open-label Study MEM-MD-91, or * completed the double-blind Study MEM-MD-68, or * discontinued study MEM-MD-68 by meeting requirements for loss of therapeutic response 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 The decision to close the study early was based on data from 2 double-blind placebo-controlled studies (MEM-MD-57A and MEM-MD-68) that failed to demonstrate a statistically significant difference between memantine and placebo in the primary efficacy parameter based on Social Responsiveness Scale (SRS) total raw score.
Interventions
During the 6-week double-blind dosing titration/maintenance period, Memantine extended-release 3-mg and 6-mg capsules; oral administration. Dosing was once daily. During open-label treatment: Memantine extended-release 3mg capsules; oral administration. The maximum target dosage was identified during the prior studies for each patient. Dosing was once daily.
Sponsors
Forest Laboratories
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* Patients who completed Study MEM-MD-67, MEM-MD-68, MEM-MD-91, or discontinued Study MEM-MD-68 due to meeting the criterion for loss of therapeutic response. * Having normal results from a physical examination and laboratory tests at Visit 1 of this study (last visit of the preceding study). Any abnormal findings must be deemed not clinically significant by the Investigator and documented as such. * 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
Exclusion criteria
* Patients who discontinued a preceding memantine study due to an adverse event possibly related to study drug * 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, 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 Columbia-Suicide Severity Rating Scale (C-SSRS) or any suicidal behavior
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patients With Any Treatment-emergent Adverse Event | Visit 1 (Week 0) up to 30 days after Visit 8 (up to Week 48) or Final Visit | Number of patients who experienced 1 or more Treatment Emergent Adverse Event |
Countries
Belgium, Canada, Colombia, Estonia, France, Hungary, Iceland, Italy, New Zealand, Poland, Serbia, South Africa, South Korea, Spain, Ukraine, United States
Participant flow
Recruitment details
Patient recruitment occurred over an eleven month period, from October of 2012 to September of 2013, at 106 study sites, located in the United States and 15 other countries.
Participants by arm
| Arm | Count |
|---|---|
| Memantine To maintain the blind of the preceding study, patients who participated in MEM-MD-68 began this study with 6 weeks of double blind dosing during which all patients were either titrated to or remained on their maximum target dosages. This was followed by up-to 42 weeks of open-label dosing.
Patients who took open-label memantine in the preceding study, MEM-MD-67 or MEM-MD-91, received up to 48 weeks of open-label memantine at their maximum tolerated weight based target dosage. | 747 |
| Total | 747 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 17 |
| Overall Study | Inclusion/exclusion not meet | 1 |
| Overall Study | Lack of Efficacy | 9 |
| Overall Study | Lost to Follow-up | 19 |
| Overall Study | Other Reason | 1 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Study Terminated by Sponsor | 582 |
| Overall Study | Withdrawal by Subject | 35 |
Baseline characteristics
| Characteristic | Memantine |
|---|---|
| Age, Continuous | 9.0 years STANDARD_DEVIATION 1.9 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 participants |
| Race/Ethnicity, Customized Asian | 44 participants |
| Race/Ethnicity, Customized Black or African American | 42 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 88 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 3 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 659 participants |
| Race/Ethnicity, Customized Other Race | 20 participants |
| Race/Ethnicity, Customized White | 636 participants |
| Region of Enrollment Belgium | 4 participants |
| Region of Enrollment Canada | 1 participants |
| Region of Enrollment Colombia | 8 participants |
| Region of Enrollment Estonia | 5 participants |
| Region of Enrollment France | 9 participants |
| Region of Enrollment Hungary | 14 participants |
| Region of Enrollment Iceland | 5 participants |
| Region of Enrollment Italy | 6 participants |
| Region of Enrollment Korea, Republic of | 22 participants |
| Region of Enrollment New Zealand | 1 participants |
| Region of Enrollment Poland | 36 participants |
| Region of Enrollment Serbia | 21 participants |
| Region of Enrollment South Africa | 1 participants |
| Region of Enrollment Spain | 14 participants |
| Region of Enrollment Ukraine | 14 participants |
| Region of Enrollment United States | 586 participants |
| Sex: Female, Male Female | 120 Participants |
| Sex: Female, Male Male | 627 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 150 / 747 |
| serious Total, serious adverse events | 8 / 747 |
Outcome results
Primary
Patients With Any Treatment-emergent Adverse Event
Number of patients who experienced 1 or more Treatment Emergent Adverse Event
Time frame: Visit 1 (Week 0) up to 30 days after Visit 8 (up to Week 48) or Final Visit
Population: Analysis was performed on the 747 patients who took at least 1 dose of investigational product (Safety Population).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Memantine | Patients With Any Treatment-emergent Adverse Event | 424 participants |