Xanamem™ in Healthy Elderly Subjects
Condition: Safety; Peripheral Neuropathy; Cortisol; Central Nervous System; Cognitive Function; Healthy Ageing; Small Fibre Neuropathy; Cerebrospinal Fluid; Electrocardiography
MeSH terms: Peripheral Nervous System Diseases; Small Fiber Neuropathy
Study type: Interventional
Phase: Phase 1

Summary: 
      Xanamem™ is being developed as a potential drug for Alzheimer's disease. This study drug has
      been designed to change the cortisol levels in the brain. Cortisol is a naturally occurring
      hormone in the body. It is believed that reducing the level of cortisol will be a benefit in
      the treatment of Alzheimer's disease.

      The XanaHES study is testing the safety and tolerability of Xanamem. It is planned to enrol
      approximately 84 participants, male and female aged from 50 to 75 who are in good health, in
      the study at 1 centre in Australia.

      The XanaHES Phase I study is a single-blind study. Subjects will be randomised to receive
      either 20mg once daily Xanamem or Placebo in cohort 1. Once all subjects have completed the
      study treatment of 12 weeks, a dose escalation committee will decide if a new cohort, cohort
      2, with 30mg once daily vs placebo is started.
    

Detailed description: 
      This is a Phase I, randomised, single-centre, single-blind, placebo-controlled study to
      assess the safety, tolerability of oral Xanamem once daily in healthy elderly subjects.

      It is planned to randomise approximately 84 subjects, 42 in each cohort, at a single site in
      Australia.

      Cohort 1 starts with a 20mg QD dose vs matching placebo. A Dose Escalation Committee will
      review the results from cohort 1 and provide a recommendation to proceed with Cohort 2
      randomisation which involves a dose escalation to 30mg.

      At the Baseline visit (Week 0), eligible subjects will be randomised on a 30:12 ratio to
      receive either Xanamem administered orally QD (treatment group) or matching placebo (placebo
      group). Subjects will return to the study site for visits at Week 2, Week 4, Week 6, Week 8,
      Week 10, End of Treatment (Week 12) and Follow-up (4 weeks post last dose of study drug)
      visits, at which study assessments will be performed.

      Ad hoc telephone contact may also occur at any other time-point throughout the study, if
      deemed necessary by the investigator/study nurse, or if the subject wishes to report an
      adverse event (AE).

      Subjects will be interviewed and examined at the study site at each visit and will complete a
      variety of questionnaires, routine safety evaluations and nerve function tests.

      A central reader will review every Nerve Function Monitoring (NFM) assessment performed for
      each subject for Potential Nerve Safety Signals (PNSS).

      Optional cerebrospinal fluid (CSF) sampling will be performed at baseline and end of
      treatment visits for a small subgroup of subjects, who provide additional consent. Subjects
      who do not provide consent for this optional sub-study will still be eligible for the main
      study.

      The overall study duration for an individual subject will be 17 to 20 weeks, including a
      screening period of up to 4 weeks, a single-blind treatment period of 12 weeks, and a
      follow-up period of 4 weeks. The total duration of the study is expected to be 1.5 years.
    

Intervention name(s): Xanamem; Matching Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Oral Xanamem capsules 20mg or 30mg, administered PO once daily. 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.; Matching placebo which is identical in appearance to the test product (20mg, 30mg Xanamem™ QD) except that it contains no active ingredient.
Other intervention name(s): UE2343; Placebo
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: A Dose Escalation Committee will review the results from Cohort 1 (20 mg active vs. placebo arms) and provide a recommendation to proceed with Cohort 2 (30 mg active vs. placebo arms) randomisation which involves a dose escalation.
Masking: Single (Participant)
Primary purpose: Other
Keywords: Actinogen; Xanamem; UE2343; Cortisol; 11β-HSD1; 11-beta-Hydroxysteroid Dehydrogenase Type 1; Healthy Ageing; Peripheral Neuropathy; Safety; Dose Escalation; Elderly; XanaHES