A Phase I, single ascending dose (SAD), randomised, double-blind, placebo-controlled study was successfully completed in 2013 with 48 healthy human volunteers. Xanamem was well tolerated with no serious adverse events, and demonstrated potent effects on pharmacodynamics biomarkers, consistent with substantial inhibition of 11B-HSD1 for at least 24 hours after a single dose.
A second Phase I study, a multiple ascending dose (MAD), randomised, double-blind, placebo-controlled study in 40 healthy volunteers was successfully completed in 2015. Participants were given doses of 10mg, 20mg and 35mg Xanamem twice daily for nine days, and once on the morning of the tenth day (19 doses in total). The primary endpoint of the study confirmed the safety and tolerability of Xanamem. Additionally, the trial demonstrated how the body absorbs and metabolises Xanamem and helped define the optimal dose for the drug for future studies.
Two additional sub-studies included a fed-fasted study to confirm the effect of food on the absorption of Xanamem, and a CNS pharmacokinetic study. This key CNS sub-study confirmed Xanamem efficiently crosses the blood-brain barrier in concentrations that would adequately inhibit the excess production of cortisol in the hippocampus and frontal cortex of the brain, Xanamem’s primary site of action.
This Multiple Ascending Dose (MAD) study was conducted by Linear Clinical Research, a world-class clinical trial facility that is part of the QEII Medical Centre in Perth, Australia.
With the initiation of XanADu, we are now in the important next stage of Xanamem’s development. XanADu is a Phase-II trial to prove the effectiveness of Xanamem in patients with Alzheimer’s disease.
All the required studies to confirm that Xanamem is well tolerated with an acceptable safety profile to proceed into Phase II have been conducted. The studies also confirmed that Xanamem crosses the blood-brain-barrier in concentrations to adequately inhibit production of cortisol in the hippocampus and frontal cortex of the brain, its primary site of action.
In 2016, Actinogen Medical initiated XanADu, a Phase II efficacy and safety trial of Xanamem in patients with mild Alzheimer’s disease. XanADu is a double-blind, randomised, placebo-controlled study of 174 patients conducted at 20 sites across Australia, UK and USA. Patient recruitment and treatment commenced in 2017 with top-line results expected in early 2019. Some of the design features are provided in the table below.
Further information and updates on XanADu, can be found at Clinicaltrials.gov (identifier: NCT02727699).
For many years, raised cortisol has been recognised as a feature of diabetes, and Type 2 diabetes in particular. Unfortunately, drugs developed to reduce cortisol levels as a treatment for diabetes have not been successful, showing little clinical benefit. A small pilot study demonstrated a potential cognitive benefit in diabetics through inhibiting excess cortisol production. Individuals with Type 2 diabetes have twice the risk of developing dementia than the general population. Our collaborators at the University of Edinburgh are interested in exploring these observations further. Discussions between Actinogen Medical and the University of Edinburgh for a Phase II trial of Xanamem in Diabetes Cognitive Impairment, partially supported by Actinogen, are ongoing.
Type 2 Diabetes is a chronic disease that affects over 422 million people globally. Current treatments control blood glucose levels but have no effect on preventing dementia. If effective, Xanamem could have an enormous impact on the global burden of this disease.
Actinogen Medical is open to receiving expressions of interest from academic and commercial parties looking to develop research partnerships in Actinogen’s focus areas.
In particular, Actinogen is seeking commercial partners to co-invest in the clinical development of Xanamem in secondary indications.
Actinogen is open to receiving both private or public capital investment to support its R&D strategy.