FROM THE LAB TO THE CLINIC:
EARLY PHASE CLINICAL RESEARCH IN HUMANS

Phase 1 – Single Ascending Dose (SAD)

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.

More information on this completed Phase I study of Xanamem in healthy subjects can be found at Clinicaltrials.gov (Identifier: NCT02616445) and in Webster et al 2017.

Phase 1 – Multiple Ascending Dose (MAD)

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.

More information on this completed Phase I Study of Xanamem in healthy subjects can be found at Clinicaltrials.gov (Identifier: NCT02616445) and Webster et al 2017.