A Phase II Study to Assess the Safety, Tolerability and Efficacy of Xanamem™ in Subjects With Mild Dementia Due to AD (XanADu)
Condition: Dementia, Alzheimer Type
MeSH terms: Alzheimer Disease; Dementia
Intervention: Xanamem™; Placebo (for Xanamem™)
Intervention description: Xanamem™ is formulated in green and cream coloured size 3, Coni-Snap shaped gelatin capsules as an excipient blend at a dose of 10mg. It contains active pharmaceutical ingredient of UE2343; Excipient blend capsules manufactured to mimic Xanamem™ capsules
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 185.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No
Keywords: Dementia; Alzheimer's Disease; Xanamem; UE2343 (Laboratory Code for Xanamem); Cortisol; XanADu; Actinogen; 11β-HSD1; 11-beta-Hydroxysteroid Dehydrogenase Type 1; Mild Alzheimer's Disease; Cognitive Impairments

Summary:

      This XanADu Phase II study in mild Alzheimer's Disease (AD) is to assess the safety,
      tolerability and efficacy of Xanamem™ in subjects with mild dementia due to Alzheimer's
      Disease. Subjects will be randomized to receive either 10mg once daily Xanamem™ or Placebo at
      a 1:1 ratio in a double-blinded fashion.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Males and females aged 50 years or older at the time of informed consent.

          2. Female Subjects:

               1. 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.

               2. 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.

               3. Are permanently sterile or have had a hysterectomy, bilateral salpingectomy or
                  bilateral oophorectomy.

               4. Women must not be breastfeeding.

          3. Male Subjects:

               1. 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.

               2. Who are permanently sterile or have had bilateral orchiectomy.

          4. 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.

          5. Mild dementia due to probable AD with Mini-Mental Status Examination (MMSE) 20 to 26
             (inclusive).

          6. Clinical Dementia Rating Scale (CDR) Global Score of 0.5 to 1.0.

          7. 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.

          8. 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.

          9. 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.

         10. 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.

         11. Must be willing and able to comply with the requirements of the protocol and must be
             available to complete the study.

         12. Must satisfy a medical examiner about their fitness to participate in the study.

         13. Must provide written informed consent to participate in the study.

        Exclusion Criteria:

          1. Clinically significant abnormalities in vital signs (blood pressure, heart rate,
             respiration rate and oral temperature), as determined by the investigator.

          2. 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.

          3. Has had a significant systematic illness or infection within the past 4 weeks prior to
             randomisation, as determined by the investigator.

          4. Clinically significant neurological disease other than AD, such as (but not limited
             to) Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure
             hydrocephalus, brain tumour, progressive supranuclear palsy, seizure disorder,
             subdural haematoma, multiple sclerosis or a history of significant head trauma
             followed by persistent neurologic defaults or known structural brain abnormalities.

          5. Subjects with clinical evidence of peripheral neuropathy or historical evidence of
             clinically significant nerve conduction abnormalities.

          6. Has had a stroke within the year prior to randomisation, as determined by the
             investigator.

          7. Has a lifetime diagnosis of a major psychiatric disorder (other than dementia), based
             on the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria.
             This includes but is not limited to schizophrenia, schizoaffective disorder, bipolar
             affective disorder, alcohol dependence syndrome or major depressive disorder.

          8. Has a history of disease directly related to the hypothalamus, the pituitary and/or
             the adrenal glands which affect the hypothalamic-pituitary-adrenal axis function.

          9. Has uncontrolled clinical conditions relating to glucose and lipid metabolism.

         10. Clinically significant electrocardiogram (ECG) abnormalities, including Corrected QT
             interval (QTc) > 450 ms, following ECG tracings at Screening.

         11. Use of any prohibited medication as detailed in the study protocol.

         12. Participation in another clinical study of an investigational drug or device whereby
             the last investigational drug/device administration is within 60 days of Screening.

         13. Inability to communicate well with the investigator (i.e. language problem, non-fluent
             English [as scales will be provided in English only], poor mental development or
             impaired cerebral function).

         14. Subject will undergo the tests, Alzheimer's Disease Assessment Scales (ADAS)-Cog v14,
             CDR-Sum of Boxes (SOB), MMSE, Neuropsychological Test Battery (NTB; executive domain)
             and RAVLT at the indicated time-points to avoid uncontrolled learning effects.
             Subjects who need to perform these tests externally to and in parallel with this study
             will be excluded.

         15. Subject has ingested any food or drink containing grapefruit, Seville oranges, star
             fruit or derived products (e.g. fruit juice), for at least 3 days prior to the first
             administration of study drug.