A Phase II Study to Assess the Safety, Tolerability and Efficacy of Xanamem™ in Subjects With Mild Dementia Due to AD (XanADu)

Inclusion Criteria

• Males and females aged 50 years or older at the time of informed consent.
• Female Subjects:
• Post menopausal women, defined as no menses for 12 months without an alternative medical cause. If there is any concern about the menopausal status of a prospective female subject, a follicle stimulating hormone test (FSH) should be requested to confirm post-menopausal status. Post menopausal women confirmed by FSH level > 40 mIU (milli-international units per milliliter) /mL, will be confirmed by central laboratory.
• Women of childbearing potential (WOCBP) must have a negative pregnancy test at Screening and Baseline, and be willing to use highly effective methods of contraception from the Screening visit until 3 months after last dose of study drug. If re-test is required, a local urine pregnancy test will be performed at Baseline to determine if the subject can continue to randomisation.
• Are permanently sterile or have had a hysterectomy, bilateral salpingectomy or bilateral oophorectomy.
• Women must not be breastfeeding.
• Male Subjects:
• Who are sexually active, fertile men must use highly effective methods of contraception from Day 1 until 3 months after last dose of study drug if their partners are WOCBP.
• Who are permanently sterile or have had bilateral orchiectomy.
• Diagnosis of mild dementia due to Alzheimer's disease (AD) with increased level of certainty (provided by evidence of clinical deterioration within the 6 months preceding Screening, as assessed by the investigator) as determined by the National Institute of Ageing (NIA) and the Alzheimer's Association (AA) workgroup.
• Mild dementia due to probable AD with Mini-Mental Status Examination (MMSE) 20 to 26 (inclusive).
• Clinical Dementia Rating Scale (CDR) Global Score of 0.5 to 1.0.
• A brain magnetic resonance imaging (MRI) or computed tomography (CT) scan in the 12 months preceding Screening that in the investigator's opinion is consistent with AD as the principle aetiology of the dementia with no other clinically significant abnormality, e.g. another principle underlying aetiology of the subject's dementia, or a lesion which could affect cognition e.g. a brain tumour or large stroke.
• On stable dose of acetylcholinesterase (AChEI) and/or memantine (at least 3 months prior to Screening) OR treatment-naïve. Initiating AChEIs or memantine during the study will not be permitted.
• Apart from a clinical diagnosis of mild dementia due to AD, the subject must be in good health as determined by the investigator, based on medical history and screening assessments.
• Has a consenting study partner who, in the investigator's judgement, has frequent and sufficient contact with the subject to be able to provide accurate information as to the subject's cognitive and functional abilities. The study partner must be available to provide information to the investigator and study site staff about the subject and agrees to attend all study site visits in person for scale completion. A study partner should be available for the duration of the study. The measure of adequate availability will be at the investigator's discretion.
• Must be willing and able to comply with the requirements of the protocol and must be available to complete the study.
• Must satisfy a medical examiner about their fitness to participate in the study.
• Must provide written informed consent to participate in the study.

Exclusion Criteria

• Clinically significant abnormalities in vital signs (blood pressure, heart rate, respiration rate and oral temperature), as determined by the investigator.
• Clinically significant abnormal haematology, biochemistry and urine examination values, specifically abnormal liver and renal function and Vitamin B12 levels below lower threshold since these parameters may impact cognitive function, as determined by the investigator.
• Has had a significant systematic illness or infection within the past 4 weeks prior to