3  Study objectives and design

3.1 Objectives

The primary objective was to characterise the dermatologic tolerability of the xanomeline transdermal therapeutic system over 24 weeks of treatment in patients with mild to moderate Alzheimer’s disease.

The secondary objective was to describe the effect of xanomeline on vital signs, expressed as change from baseline in systolic blood pressure at week 24.

3.2 Overall design

The study was a randomised, double-blind, placebo-controlled, parallel-group study conducted at multiple sites. Eligible subjects were randomised in equal proportions to placebo, xanomeline low dose or xanomeline high dose, and were treated for 24 weeks.

Assessments were scheduled at baseline and at weeks 2, 4, 6, 8, 12, 16, 20, 24 and 26. Adverse events were collected throughout the treatment period and for 30 days after the last dose.

3.3 Selection of the study population

Subjects were eligible if they had a diagnosis of probable Alzheimer’s disease of mild to moderate severity, were able to comply with the visit schedule, and had a caregiver able to support study participation. Subjects with clinically significant dermatologic conditions at the application site were excluded.

3.4 Disposition of subjects

Screened n = 306 Randomised n = 254 Treated (safety population) n = 254 Completed the study n = 110 Not randomised n = 52 Not treated n = 0 Discontinued n = 144

Figure 14.1.1: Disposition of subjects from screening to study completion [Schulz et al. (2010)].