TSFAE15:	Subjects With Treatment-emergent Adverse Events Leading to Discontinuation of Study Treatment  by System Organ Class and FDA Medical Query (Narrow); Safety Analysis Set (Study jjcs - core)							
 	Active Study Agent 	Active Study Agent 	Active Study Agent 	 	Risk Difference (%) (95% CI) 	Risk Difference (%) (95% CI) 	
Organ Systema 	Xanomeline High Dose 	Xanomeline Low Dose 	Combined 	Placebo 	Xanomeline High Dose vs Placebo 	Xanomeline Low Dose vs Placebo 	
  OCMQ (Narrow), n (%) 	N=53 	N=73 	N=126 	N=59 	  	  	
Skin and subcutaneous tissue disorders 	9 (17.0%) 	6 (8.2%) 	15 (11.9%) 	4 (6.8%) 	10.2 (-1.8, 22.2) 	1.4 (-7.6, 10.4) 	
Pruritus 	5 (9.4%) 	5 (6.8%) 	10 (7.9%) 	1 (1.7%) 	7.7 (-0.8, 16.3) 	5.2 (-1.5, 11.8) 	
Rash 	3 (5.7%) 	1 (1.4%) 	4 (3.2%) 	1 (1.7%) 	4.0 (-3.1, 11.0) 	-0.3 (-4.6, 3.9) 	
Erythema 	2 (3.8%) 	1 (1.4%) 	3 (2.4%) 	2 (3.4%) 	0.4 (-6.5, 7.3) 	-2.0 (-7.4, 3.3) 	
 	 	 	 	 	 	 	
General disorders and administration site conditions 	4 (7.5%) 	4 (5.5%) 	8 (6.3%) 	3 (5.1%) 	2.5 (-6.6, 11.5) 	0.4 (-7.3, 8.1) 	
Dizziness 	1 (1.9%) 	3 (4.1%) 	4 (3.2%) 	0 	1.9 (-1.8, 5.5) 	4.1 (-0.4, 8.7) 	
Fatigue 	2 (3.8%) 	1 (1.4%) 	3 (2.4%) 	0 	3.8 (-1.4, 8.9) 	1.4 (-1.3, 4.0) 	
Local Administration Reaction 	1 (1.9%) 	0 	1 (0.8%) 	1 (1.7%) 	0.2 (-4.7, 5.1) 	-1.7 (-5.0, 1.6) 	
Decreased Appetite 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
Peripheral Edema 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
 	 	 	 	 	 	 	
Nervous system disorders 	4 (7.5%) 	1 (1.4%) 	5 (4.0%) 	1 (1.7%) 	5.9 (-2.0, 13.7) 	-0.3 (-4.6, 3.9) 	
Headache 	2 (3.8%) 	0 	2 (1.6%) 	0 	3.8 (-1.4, 8.9) 	0.0 (0.0, 0.0) 	
Syncope 	1 (1.9%) 	1 (1.4%) 	2 (1.6%) 	0 	1.9 (-1.8, 5.5) 	1.4 (-1.3, 4.0) 	
Confusional State 	1 (1.9%) 	0 	1 (0.8%) 	1 (1.7%) 	0.2 (-4.7, 5.1) 	-1.7 (-5.0, 1.6) 	
 	 	 	 	 	 	 	
Infections and infestations 	2 (3.8%) 	1 (1.4%) 	3 (2.4%) 	4 (6.8%) 	-3.0 (-11.2, 5.2) 	-5.4 (-12.4, 1.5) 	
Nasopharyngitis 	2 (3.8%) 	1 (1.4%) 	3 (2.4%) 	3 (5.1%) 	-1.3 (-8.9, 6.3) 	-3.7 (-9.9, 2.5) 	
Bacterial Infection 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
 	 	 	 	 	 	 	
Vascular disorders 	2 (3.8%) 	1 (1.4%) 	3 (2.4%) 	0 	3.8 (-1.4, 8.9) 	1.4 (-1.3, 4.0) 	
Hemorrhage 	1 (1.9%) 	1 (1.4%) 	2 (1.6%) 	0 	1.9 (-1.8, 5.5) 	1.4 (-1.3, 4.0) 	
Thrombosis 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
Thrombosis Arterial 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
 	 	 	 	 	 	 	
Cardiac disorders 	1 (1.9%) 	1 (1.4%) 	2 (1.6%) 	0 	1.9 (-1.8, 5.5) 	1.4 (-1.3, 4.0) 	
Acute Coronary Syndrome 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
Myocardial Infarction 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
Myocardial Ischemia 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
Palpitations 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
 	 	 	 	 	 	 	
Gastrointestinal disorders 	0 	2 (2.7%) 	2 (1.6%) 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	1.0 (-3.9, 6.0) 	
Diarrhea 	0 	2 (2.7%) 	2 (1.6%) 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	1.0 (-3.9, 6.0) 	
Vomiting 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
 	 	 	 	 	 	 	
Respiratory, thoracic and mediastinal disorders 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
Dyspnea 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
 	 	 	 	 	 	 	
Immune system disorders 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
Hypersensitivity 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
 	 	 	 	 	 	 	
Renal and urinary disorders 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
Renal & Urinary Tract Infection 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	

Key: FMQ=FDA Medical Query 	
Key: FMQ=FDA Medical Query	
Key: FMQ=FDA Medical Query	
Key: FMQ=FDA Medical Query	
Key: FMQ=FDA Medical Query	
Key: FMQ=FDA Medical Query	
Key: FMQ=FDA Medical Query	
a Each FMQ is aligned to a single system organ class based on clinical judgment, as defined by FDA. However, some FMQs may contain preferred terms from more than one system organ class. 	a Each FMQ is aligned to a single system organ class based on clinical judgment, as defined by FDA. However, some FMQs may contain preferred terms from more than one system organ class.	a Each FMQ is aligned to a single system organ class based on clinical judgment, as defined by FDA. However, some FMQs may contain preferred terms from more than one system organ class.	a Each FMQ is aligned to a single system organ class based on clinical judgment, as defined by FDA. However, some FMQs may contain preferred terms from more than one system organ class.	a Each FMQ is aligned to a single system organ class based on clinical judgment, as defined by FDA. However, some FMQs may contain preferred terms from more than one system organ class.	a Each FMQ is aligned to a single system organ class based on clinical judgment, as defined by FDA. However, some FMQs may contain preferred terms from more than one system organ class.	a Each FMQ is aligned to a single system organ class based on clinical judgment, as defined by FDA. However, some FMQs may contain preferred terms from more than one system organ class.