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

- 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.

- 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.