Efficacy and Safety of Memantine Hydrochloride in Enhancing the Cognitive Abilities of Young Adults With Down Syndrome

Inclusion Criteria:

• Males or females with Down syndrome aged 18 to 32 years. The documented cytogenetic diagnosis should be either "Trisomy 21", or "Complete Unbalanced Translocation of the Chromosome 21".
• Female subjects must be documented not to be pregnant by serum testing at screening.
• Laboratory findings within normal limits or judged clinically insignificant at baseline.
• Vital signs must be within normal limits for their age. (Medically treated hypotension will be allowed.)
• Screening ECG must demonstrate predominately normal sinus rhythm. Minor abnormalities documented as clinically insignificant by the investigator will be allowed. (Subjects with clinically significant but stable ECG abnormalities may enter the trial only with the permission of the principal investigators.)
• Subjects and their authorized representative will provide written informed consent and assessment.
• Subjects who have been receiving any experimental drug for Down syndrome must undergo a washout (~ 30 days or five half-lives of the drug, whichever is longer).
• Sufficiently proficient in English to be capable of reliably completing study assessments.
• Able to swallow oral medication (crushing of tablets will not be permitted).
• Must have a reliable caregiver or family member who agrees to accompany the subject to all visits, provide information about the subject as required by this protocol, and ensure compliance with the medication schedule. The subject must have contact at least once a day with the caregiver.
• Generally good health and judged by the investigators to be able to fully participate in the trial.

Exclusion Criteria:

• Subjects weighing less than 40 kg.
• Any current psychiatric or neurologic diagnosis other than Down syndrome.
• Subjects who currently meet or have within the past five years met DSM-IV (Diagnostic and Statistical Manual) criteria for drug or alcohol abuse or dependence.
• Subjects who, in the judgment of the investigators, currently represent a significant suicide risk or who would require treatment with electro-convulsive therapy or with psychotropic drugs during the study or who have received treatment with a depot neuroleptic drug within 6 months of entering the study.
• Subjects who are hospitalized or residing in a skilled nursing facility or subjects who are anticipated to enter a nursing home within the next 6 months. (Subjects may reside in group homes of other residential settings where they do not require or receive skilled nursing.)
• Any active or clinically significant conditions affecting absorption, distribution or metabolism of the study drugs.
• Subjects with significant allergies to or other significant intolerance of memantine therapy, its ingredients, or with contraindications to memantine therapy as stated in the prescribing information.
• Subjects who are expected to require general anesthetics during the course of the study.
• History or presence of seizure disorder (less than 3 years) or encephalitis.
• History of malignant neoplasms treated within 3 years prior to study entry or where there is current evidence of recurrent or metastatic disease.
• Subjects with treated hypothyroidism must be on a stable dose of medication for at least 3 months prior to screening and have normal serum T-4 and thyroid-stimulating hormone at screening. Subjects with diabetes mellitus controlled by diet, oral medication or insulin must have an HbA1c of < 8.0% and random serum glucose value of < 170 mg/dl.
• Severe infections or a major surgical operation within 3 months prior to screening.
• History of persistent cognitive deficits immediately following head trauma.
• Subjects who have donated blood or blood products during the 30 days prior to screening who plan to donate blood while participating in the study or within four weeks after completion of the study.
• Subjects who may not be able to comply with the protocol or perform the outcomes measures due to significant hearing or visual impairment or other issues judged relevant by the investigators.