9  Discussion and overall conclusions

Over 24 weeks of double-blind treatment in 254 subjects with mild to moderate Alzheimer’s disease, the dermatologic tolerability of the xanomeline transdermal therapeutic system was the dominant safety finding. 98 subjects reported at least one dermatologic treatment-emergent adverse event, and the events began earlier in both xanomeline groups than in the placebo group.

Serious treatment-emergent adverse events were reported for 3 subjects, without a pattern suggesting a treatment-related excess. Laboratory, vital sign and electrocardiogram findings did not identify a new safety concern, no subject in a xanomeline group met the combined biochemical criterion for potential drug-induced liver injury, and systolic blood pressure was unchanged relative to placebo at week 24.

The results support the conclusion that dermatologic tolerability is the limiting factor for this formulation at the doses studied. Any further development of the transdermal route should address application-site tolerability, for example by modifying the adhesive system or the rotation schedule of application sites.

This report is a demonstration of Quarto for regulated reporting. The conclusions describe the public CDISC pilot data used to build it and are not a statement about any real medicinal product.