Prazosin for Agitation in Alzheimer's Disease

Inclusion Criteria

Participants must meet all of the following criteria be included in the study:

• Men and women with probable or possible AD by NINCDS-ADRDA criteria utilizing history; medical records review; physical and neurological exam; and laboratory tests (as applicable). Brain neuroimaging is not a requirement.
• Participants must either reside in an LTC that is associated with the study site or at home with full-time caregiving.
• Participants must have disruptive agitation significant enough to disrupt caregiving and, in the opinion of the Site Principal Investigator, to justify treatment. Disruptive agitation, defined as having any combination of the following target behaviors, must have occurred nearly daily during the previous week and at least intermittently for 4 weeks prior to screening:
• irritability,
• physically and/or verbally aggressive behavior,
• physical resistiveness to necessary care
• pressured motor activity (e.g., pressured pacing) These behaviors must be problematic in that they cause participant and caregiver distress and/or interfere with essential care or disrupt their living environment. Target behaviors may be any combination of the listed domains. Disruptive agitation must meet this threshold at Screening, documented on the Behavioral Inclusion Criteria Checklist.
• Psychotropic medication, if used, should be stable for at least 2 weeks prior to randomization.
• If taking cholinesterase inhibitor and/or memantine, must be on stable dose for 3 months prior t o randomization.
• During the week before randomization, the above-described behaviors of eligible participants must be rated as of at least moderate severity.

Exclusion Criteria

Participants meeting any of the following criteria must not be included in the study:

• History of schizophrenia, schizoaffective disorder, or bipolar disorder according to the criteria of the most current version of the Diagnostic and Statistical Manual of Mental Disorders (DSM).
• Other neurodegenerative diseases, including Parkinsons disease and Huntingtons disease, or cerebral tumor.
• Dementia other than probable or possible AD per NINCDS-ADRDA criteria, such as human immunodeficiency virus (HIV) dementia, Creutzfeldt-Jakob disease, frontotemporal dementia, multiple cerebral infarctions, or normal pressure hydrocephalus.
• Current treatment for seizure disorder (Note: anticonvulsants prescribed for disruptive agitation in the absence of seizure disorder will be allowed).
• Abnormal laboratory values with clinical significance in the opinion of the site Principal Investigator.
• Current unstable medical illness including delirium, worsening congestive heart failure, unstable angina, recent myocardial infarction (within the past 3 months), acute infectious disease, severe renal or hepatic failure, severe respiratory disease, metastatic cancer, or other conditions that, in the Site Principal Investigators opinion, could interfere with the analyses of safety and efficacy in this study.
• Bedbound; participants may be ambulatory or use a wheelchair.
• Absence of any comprehensible language.
• Participation in another clinical trial for an investigational agent and took at least one dose of study drug (unless unblinded on placebo) within 12 weeks prior to screening. (The end of a previous investigational trial is defined as the date of the last dose of an investigational agent).
• Preexisting recurrent hypotension (systolic BP 20 mmHg drop in systolic BP following 2 minutes of standing posture [or sitting if unable to stand] and accompanied by dizziness, lightheadedness, or syncope).
• A 2-week washout is required prior to BL for the following exclusionary medications: prazosin or other alpha-1 blocker, sildenafil, vardenafil, tadalafil, and avanafil.
• Women of childbearing potential are not included in this study. Women of non-childbearing potential are defined as any of the following:
• have been postmenopausal (no menstrual