An Efficacy and Safety Trial of MK-8931 in Mild to Moderate Alzheimer's Disease (P07738 AM3) (EPOCH)

Inclusion Criteria:

• Diagnosis of probable AD based on both a) the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria and b) the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria for AD
• AD is of mild to moderate severity
• Clear history of cognitive and functional decline over at least one year that is either a) documented in medical records or b) documented by history from an informant who knows the subject well
• Able to read at a 6th grade level or equivalent, and must have a history of academic achievement and/or employment sufficient to exclude mental retardation
• If a participant is receiving an acetylcholinesterase inhibitor, memantine and/or herbal medications for AD, the dose must have been stable for at least three months before Screening, and the participant must be willing to remain on the same dose for the duration of the trial
• Participant must have a reliable and competent trial partner/caregiver who must have a close relationship with the subject

Exclusion Criteria:

• History of stroke
• Evidence of a neurological disorder other than the disease being studied (ie, probable AD)
• History of seizures or epilepsy within the last 5 years before Screening
• Evidence of a clinically relevant or unstable psychiatric disorder, excluding major depression in remission
• Participant is at imminent risk of self-harm or of harm to others
• History of alcoholism or drug dependency/abuse within the last 5 years before Screening
• Participant is unwilling or not eligible to undergo a magnetic resonance imaging (MRI) scan
• History of hepatitis or liver disease that has been active within the six months prior to Screening Visit
• Recent or ongoing, uncontrolled, clinically significant medical condition within 3 months of the Screening Visit (e.g., diabetes, hypertension, thyroid or endocrine disease, congestive heart failure, angina, cardiac or gastrointestinal disease, dialysis, or abnormal renal function) other than the condition being studied such that participation in the trial would pose a significant medical risk to the subject. Controlled co-morbid conditions are not exclusionary if stable within three months of the Screening Visit
• History or current evidence of long QT syndrome, corrected QT (QTc) interval ≥470 milliseconds (for male subjects) or ≥480 milliseconds (for female subjects), or torsades de pointes
• History of malignancy occurring within the five years before Screening, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or localized prostate carcinoma; or malignancy which has been treated with potentially curative therapy with no evidence of recurrence for ≥3 year post-therapy
• Clinically significant vitamin B12 or folate deficiency in the six months before Screening Visit
• Use of any investigational drugs or participation in any other clinical trial within the 30 days before Screening Visit
• History of a hypersensitivity reaction to more than three drugs
• Has tested positive for human immunodeficiency virus (HIV)
• Close family member (including the caregiver) who is among the personnel of the investigational or sponsor staff directly involved with this trial

Additional Exclusion Criteria for Safety Cohort (first approximately 400 participants entering trial):

• History of an ongoing medical condition that has been poorly controlled within 6 months of the Screening Visit (e.g., syncope, hypotension, diabetes, hypertension, cerebrovascular disease, thyroid disease, endocrine disturbance, congestive heart failure, cardiac or gastrointestinal disease, dialysis, or abnormal renal function) other than the condition being studied such that a subject's participation in the trial would pose a significant medical risk
• History of congestive heart failure (moderate or greater severity), myocardial infarction, heart surgery, syncope, bradycardia, or clinically significant hypotension within one year before Screening