A Phase 2a Study to Evaluate the Effect of Rilapladib (SB-659032) in Alzheimer's Disease

Inclusion Criteria

• A clinical diagnosis of possible Alzheimer's disease in accordance with the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria, with radiological (Magnetic Resonance Imaging [MRI] or Computed Tomography [CT]) evidence of significant cerebrovascular disease (CVD), assessed within the last 12 months
• Male or female between 50 and 80 years of age inclusive, at the time of signing the informed consent.
• Subject has a documented history of at least 6 months of ongoing Alzheimer's disease therapy (AChEIs and/or memantine) with stable dosing for at least the last 2 months (and with no intent to change for the duration of the study).
• Mini-Mental Status Examination (MMSE) score between 20 and 26 at Screening.
• Clinical Dementia Rating Scale (CDR) score of 0.5 or 1.0 at Screening.
• A female subject is eligible to participate if she is of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea; or of child-bearing potential and agrees to use acceptable contraception methods
• Subject has provided full written informed consent prior to the performance of any protocol-specified procedure; or if the subject is unable to provide informed consent due to cognitive status, the subject will provide assent and full written informed consent will be provided by a legally acceptable representative
• The subject has a dedicated caregiver who is willing to supervise participation in the study
• In the opinion of the investigator, the subject has the ability to comply with study procedures (cognitive and other testing) and is fluent in the language used for the administration of the cognitive tests.

Exclusion Criteria

• History and/or evidence of any other CNS disorder that could be interpreted as a cause of dementia: e.g. structural or developmental abnormality, epilepsy, infectious, degenerative or inflammatory/demyelinating CNS conditions such as, Parkinson's disease and frontotemporal dementia
• History of significant psychiatric illness such as schizophrenia or bipolar affective disorder that in the opinion of the Investigator would interfere with participation in the study; major depressive disorder (according to DSM-IV) in the past year; current active depression requiring initiation of treatment (or is believed to account for substantial degree of cognitive impairment)
• Evidence of the following disorders: current vitamin B12 deficiency, positive syphilis serology (unless neurosyphilis was ruled out) or active thyroid dysfunction (particularly suggestive of hypothyroidism), including abnormally high or low serum levels of thyroid stimulating hormone (TSH), where this is thought to be the cause of, or to contribute to the severity of the subject's dementia.
• History of alcohol or other substance abuse, according to the DSM-IV criteria, or recent or remote history of the same if that could be a contributing factor to dementia.
• History of intra cerebral haemorrhage due to any of the following causes: cerebral amyloid angiopathy, uncontrolled hypertension, cerebral arteriovenous malformation, coagulopathy, CNS vasculitis or any other condition that the investigator and/or medical monitor considers as a relevant risk factor for intracerebral haemorrhage
• Recent (i.e., 160mmHg or diastolic blood pressure >110mmHg)
• QTcB interval >450 msec; or QTcB > 480 msec in subjects with bundle branch block based on ECG assessment at the Screening visit.
• HbA1c >12.0 at Screening, or uncontrolled diabetes in the opinion of the investigator.
• History of glaucoma or any other findings in the baseline eye exam that, in the opinion of the investigator, would exclude the subject from participation in the study.
• History of adult asthma (or reactive airway disease) manifested by bronchospasm