# Study Synopsis: CDISCPilot01

## Study Title
Safety and Efficacy of the Xanomeline Transdermal Therapeutic System (TTS) in Patients with Mild to Moderate Alzheimer's Disease

## Study Identification
- **Study ID**: CDISCPilot01
- **Phase**: Phase 2/3
- **Indication**: Alzheimer's Disease (Mild to Moderate)

## Objectives

### Primary Objective
Evaluate the efficacy of Xanomeline TTS compared to placebo on cognitive function as measured by the ADAS-Cog (11) score.

### Secondary Objectives
- Assess clinical global impression (CIBIC+)
- Evaluate behavioral symptoms (NPI-X)
- Evaluate safety and tolerability

## Study Design
Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-Center study.

## Subject Count
- **Planned**: 300 subjects (100 per group)
- **Screened**: 306 subjects
- **Randomized (ITT)**: 254 subjects
- **Efficacy**: 234 subjects
- **Safety**: 254 subjects

## Treatment Groups
| Group | Treatment | Planned N | Actual N |
|-------|-----------|-----------|----------|
| Placebo | Transdermal patch (placebo) | 100 | 86 |
| Xanomeline Low Dose | Xanomeline TTS 50 cm2 | 100 | 84 |
| Xanomeline High Dose | Xanomeline TTS 75 cm2 | 100 | 84 |

Randomization ratio: 1:1:1

## Primary Endpoint
- **Name**: Change from Baseline to Week 24 in ADAS-Cog (11) Total Score
- **Measurement**: ADAS-Cog (Alzheimer's Disease Assessment Scale - Cognitive Subscale, 11 items, score range 0-70)
- **Timepoint**: Week 24
- **Statistical Method**: ANCOVA with treatment, pooled site group, and baseline score as covariates
- **Missing Data**: LOCF (Last Observation Carried Forward)

## Analysis Populations
| Population | Definition | N |
|-----------|------------|---|
| ITT | All randomized subjects | 254 |
| Safety | Subjects who received at least one dose | 254 |
| Efficacy | Subjects with at least one post-baseline efficacy assessment | 234 |

## Study Duration
24 weeks of treatment + 2 weeks of follow-up

## Treatment Administration
Xanomeline is a selective M1 muscarinic acetylcholine receptor agonist delivered via transdermal patch for stable plasma concentrations.
