Nuedexta in the Treatment of Pseudobulbar Affect in Patients With Alzheimer's Disease

Inclusion Criteria:

• Male/female 55 to 90 years, inclusive.
• Meets National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria for probable AD.
• Modified Hachinski Ischemia Scale score of ≤4.
• Folstein Mini Mental State Exam score 16-26 at Visit 1.
• Geriatric Depression Scale score ≤6. For patient with history of depression, he/she have been on steady dose of anti-depressant for at least 3 months.
• Clinical history and relevant symptoms of Pseudobulbar Affect.
• Center for Neurologic Study-Lability Scale score at baseline ≥13.
• Stable hematologic, hepatic, and renal function, with no clinically significant symptoms, and with clinical laboratory results (CBC, clinical chemistry, and urinalysis) up to 1-fold higher than upper limit of normal range.
• Resting respiratory rate 12-20/minute.
• MRI or CT scan within past 12 months; no findings inconsistent with diagnosis of AD.
• ECG (within 4 weeks prior to entry)with no evidence of clinically significant abnormalities.
• Concurrent treatment with an acetylcholinesterase inhibitor or memantine allowed; must be on stable dose at least 2 months before screening. Dosing must remain stable throughout the study.
• Use of SSRI's allowed. Must have used for 3 months prior to study entry; dose must remain unchanged during course of study.
• No current symptoms of depressive disorder.
• Score of 19 or lower in the Beck Depression Inventory.
• Agrees to use no prohibited medications during study.

Exclusion Criteria:

• Has current serious or unstable illnesses that, in investigator's opinion, could interfere with analysis of safety and efficacy data; has life expectancy <2 years.
• No reliable caregiver in frequent contact with patient (at least 10 hours/week.
• Current or prior history of major psychiatric disturbance.
• Have been in other clinical study within 30 days of entry.
• Score of 20 or higher in Beck Depression Inventory.
• Multiple episodes of head trauma, history within last year of serious infectious disease affecting the brain, head trauma resulting in protracted loss of consciousness, or myasthenia gravis.
• Within the last 5 years, history of a primary or recurrent malignant disease.
• Known sensitivity to quinidine or dextromethorphan.
• History of human immunodeficiency virus, multiple or severe drug allergies, or severe post-treatment hypersensitivity reactions.
• History of chronic alcohol or drug abuse/dependence within the past 5 years.
• Judged by investigator to be at serious risk for suicide.
• Has a recent or current lab result indicating clinically significant lab abnormality.
• At Visit 1 has ALT/SGPT values ≥2 times upper limit of normal (ULN); AST/SGOT values ≥3 times the ULN; total bilirubin values ≥2 times the ULN.
• Resting diurnal oxygen saturation <95%.
• Received dextromethorphan and quinidine within previous 6 months.
• Hypotension (systolic BP <100 mm Hg); postural syncope; unexplained syncope.
• Used medications that affect the CNS (except for AD) for less than 4 weeks.
• On disallowed concomitant medications.
• Experiencing acute exacerbation of underlying neurological disorder within previous 2 months.