An Open-Label Safety Study of Memantine in Pediatric Patients With Autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS)

Forest Laboratories

Status and phase: Completed; Phase 2

Conditions: Asperger's Disorder; Autistic Disorder; Pediatric Autism; Autism Spectrum Disorder (ASD); Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS); Asperger's; Autism

Treatments: Drug: Memantine Hydrochloride (HCl)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01592786

MEM-MD-91

Details and patient eligibility

About

The purpose 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 a follow-up randomized withdrawal study.

Full description

This 50-week multicenter and multinational clinical study is comprised of a 2-week screening period, a 6-week open-label dose-titration period followed by a variable duration maintenance period (up to 42 weeks).

Patients with at least 12 weeks of investigational product exposure who meet the protocol specified responder criterion at two consecutive visits separated by at least two weeks are eligible to transition to a randomized withdrawal study. A responder is defined as a patient who demonstrates 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.

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 No observed adverse effect level (NOAEL) 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

Enrollment: 906 patients

Sex: All

Ages: 6 to 12 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male or female outpatients.
2. Age of 6-12.
3. Meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnostic criteria for autism, Asperger's Disorder, or Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS)
4. 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

1. Have enrolled in Study MEM-MD-57A
2. Medical conditions that might interfere with the conduct of the study, confound interpretation of the study results, or endanger the patient's well-being.
3. Participation in any other clinical investigation using an experimental drug within 30 days of screening.
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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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906 participants in 1 patient group

Memantine Hydrochloride (HCl)

Experimental group

Description:

Once daily oral administration of open-label memantine for up to 48 weeks: 6-week dose-titration period followed by up to 42-week maintenance period.

Treatment:

Drug: Memantine Hydrochloride (HCl)