TSFAE14:	Subjects With Treatment-emergent Serious Adverse Events 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 	34 (64.2%) 	28 (38.4%) 	62 (49.2%) 	11 (18.6%) 	45.5 (29.2, 61.8) 	19.7 (4.8, 34.7) 	
Pruritus 	24 (45.3%) 	21 (28.8%) 	45 (35.7%) 	6 (10.2%) 	35.1 (19.7, 50.6) 	18.6 (5.7, 31.5) 	
Erythema 	16 (30.2%) 	14 (19.2%) 	30 (23.8%) 	5 (8.5%) 	21.7 (7.5, 36.0) 	10.7 (-0.8, 22.2) 	
Rash 	10 (18.9%) 	8 (11.0%) 	18 (14.3%) 	4 (6.8%) 	12.1 (-0.2, 24.4) 	4.2 (-5.4, 13.8) 	
Urticaria 	1 (1.9%) 	1 (1.4%) 	2 (1.6%) 	0 	1.9 (-1.8, 5.5) 	1.4 (-1.3, 4.0) 	
 	 	 	 	 	 	 	
General disorders and administration site conditions 	12 (22.6%) 	16 (21.9%) 	28 (22.2%) 	7 (11.9%) 	10.8 (-3.2, 24.7) 	10.1 (-2.5, 22.6) 	
Local Administration Reaction 	5 (9.4%) 	5 (6.8%) 	10 (7.9%) 	4 (6.8%) 	2.7 (-7.5, 12.8) 	0.1 (-8.6, 8.7) 	
Dizziness 	4 (7.5%) 	4 (5.5%) 	8 (6.3%) 	0 	7.5 (0.4, 14.7) 	5.5 (0.3, 10.7) 	
Fatigue 	4 (7.5%) 	3 (4.1%) 	7 (5.6%) 	1 (1.7%) 	5.9 (-2.0, 13.7) 	2.4 (-3.2, 8.0) 	
Fall 	1 (1.9%) 	2 (2.7%) 	3 (2.4%) 	0 	1.9 (-1.8, 5.5) 	2.7 (-1.0, 6.5) 	
Peripheral Edema 	1 (1.9%) 	1 (1.4%) 	2 (1.6%) 	2 (3.4%) 	-1.5 (-7.4, 4.4) 	-2.0 (-7.4, 3.3) 	
Pyrexia 	0 	2 (2.7%) 	2 (1.6%) 	0 	0.0 (0.0, 0.0) 	2.7 (-1.0, 6.5) 	
 	 	 	 	 	 	 	
Nervous system disorders 	6 (11.3%) 	8 (11.0%) 	14 (11.1%) 	2 (3.4%) 	7.9 (-1.8, 17.6) 	7.6 (-1.0, 16.1) 	
Headache 	2 (3.8%) 	3 (4.1%) 	5 (4.0%) 	1 (1.7%) 	2.1 (-4.0, 8.2) 	2.4 (-3.2, 8.0) 	
Somnolence 	0 	4 (5.5%) 	4 (3.2%) 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	3.8 (-2.4, 10.0) 	
Confusional State 	1 (1.9%) 	1 (1.4%) 	2 (1.6%) 	1 (1.7%) 	0.2 (-4.7, 5.1) 	-0.3 (-4.6, 3.9) 	
Stroke and TIA 	0 	2 (2.7%) 	2 (1.6%) 	0 	0.0 (0.0, 0.0) 	2.7 (-1.0, 6.5) 	
Paresthesia 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
Seizure 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
Syncope 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
 	 	 	 	 	 	 	
Cardiac disorders 	6 (11.3%) 	7 (9.6%) 	13 (10.3%) 	5 (8.5%) 	2.8 (-8.3, 13.9) 	1.1 (-8.7, 10.9) 	
Arrhythmia 	4 (7.5%) 	5 (6.8%) 	9 (7.1%) 	3 (5.1%) 	2.5 (-6.6, 11.5) 	1.8 (-6.3, 9.8) 	
Acute Coronary Syndrome 	2 (3.8%) 	1 (1.4%) 	3 (2.4%) 	2 (3.4%) 	0.4 (-6.5, 7.3) 	-2.0 (-7.4, 3.3) 	
Myocardial Infarction 	2 (3.8%) 	1 (1.4%) 	3 (2.4%) 	2 (3.4%) 	0.4 (-6.5, 7.3) 	-2.0 (-7.4, 3.3) 	
Myocardial Ischemia 	2 (3.8%) 	1 (1.4%) 	3 (2.4%) 	2 (3.4%) 	0.4 (-6.5, 7.3) 	-2.0 (-7.4, 3.3) 	
Cardiac Conduction Disturbance 	0 	2 (2.7%) 	2 (1.6%) 	2 (3.4%) 	-3.4 (-8.0, 1.2) 	-0.7 (-6.6, 5.3) 	
Tachycardia 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
 	 	 	 	 	 	 	
Gastrointestinal disorders 	8 (15.1%) 	4 (5.5%) 	12 (9.5%) 	3 (5.1%) 	10.0 (-1.1, 21.2) 	0.4 (-7.3, 8.1) 	
Diarrhea 	2 (3.8%) 	2 (2.7%) 	4 (3.2%) 	1 (1.7%) 	2.1 (-4.0, 8.2) 	1.0 (-3.9, 6.0) 	
Abdominal Pain 	2 (3.8%) 	1 (1.4%) 	3 (2.4%) 	1 (1.7%) 	2.1 (-4.0, 8.2) 	-0.3 (-4.6, 3.9) 	
Vomiting 	3 (5.7%) 	0 	3 (2.4%) 	0 	5.7 (-0.6, 11.9) 	0.0 (0.0, 0.0) 	
Nausea 	2 (3.8%) 	0 	2 (1.6%) 	0 	3.8 (-1.4, 8.9) 	0.0 (0.0, 0.0) 	
Dyspepsia 	0 	1 (1.4%) 	1 (0.8%) 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-0.3 (-4.6, 3.9) 	
Constipation 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
 	 	 	 	 	 	 	
Infections and infestations 	5 (9.4%) 	5 (6.8%) 	10 (7.9%) 	7 (11.9%) 	-2.4 (-13.8, 9.0) 	-5.0 (-15.1, 5.1) 	
Nasopharyngitis 	4 (7.5%) 	3 (4.1%) 	7 (5.6%) 	5 (8.5%) 	-0.9 (-11.0, 9.1) 	-4.4 (-12.8, 4.1) 	
Bacterial Infection 	1 (1.9%) 	1 (1.4%) 	2 (1.6%) 	1 (1.7%) 	0.2 (-4.7, 5.1) 	-0.3 (-4.6, 3.9) 	
Pneumonia 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
Viral Infection 	1 (1.9%) 	0 	1 (0.8%) 	1 (1.7%) 	0.2 (-4.7, 5.1) 	-1.7 (-5.0, 1.6) 	
 	 	 	 	 	 	 	
Vascular disorders 	3 (5.7%) 	6 (8.2%) 	9 (7.1%) 	3 (5.1%) 	0.6 (-7.8, 8.9) 	3.1 (-5.3, 11.6) 	
Thrombosis 	2 (3.8%) 	3 (4.1%) 	5 (4.0%) 	2 (3.4%) 	0.4 (-6.5, 7.3) 	0.7 (-5.8, 7.2) 	
Thrombosis Arterial 	2 (3.8%) 	3 (4.1%) 	5 (4.0%) 	2 (3.4%) 	0.4 (-6.5, 7.3) 	0.7 (-5.8, 7.2) 	
Hemorrhage 	1 (1.9%) 	3 (4.1%) 	4 (3.2%) 	1 (1.7%) 	0.2 (-4.7, 5.1) 	2.4 (-3.2, 8.0) 	
Hypotension 	0 	0 	0 	2 (3.4%) 	-3.4 (-8.0, 1.2) 	-3.4 (-8.0, 1.2) 	
 	 	 	 	 	 	 	
Psychiatric disorders 	1 (1.9%) 	4 (5.5%) 	5 (4.0%) 	4 (6.8%) 	-4.9 (-12.3, 2.5) 	-1.3 (-9.6, 7.0) 	
Study Agent Abuse Potential 	0 	3 (4.1%) 	3 (2.4%) 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	2.4 (-3.2, 8.0) 	
Anxiety 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
Insomnia 	1 (1.9%) 	0 	1 (0.8%) 	1 (1.7%) 	0.2 (-4.7, 5.1) 	-1.7 (-5.0, 1.6) 	
Irritability 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
Psychosis 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
 	 	 	 	 	 	 	
Musculoskeletal and connective tissue disorders 	4 (7.5%) 	0 	4 (3.2%) 	1 (1.7%) 	5.9 (-2.0, 13.7) 	-1.7 (-5.0, 1.6) 	
Back Pain 	3 (5.7%) 	0 	3 (2.4%) 	0 	5.7 (-0.6, 11.9) 	0.0 (0.0, 0.0) 	
Arthralgia 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
Fracture 	1 (1.9%) 	0 	1 (0.8%) 	1 (1.7%) 	0.2 (-4.7, 5.1) 	-1.7 (-5.0, 1.6) 	
Osteoporosis 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
 	 	 	 	 	 	 	
Respiratory, thoracic and mediastinal disorders 	3 (5.7%) 	1 (1.4%) 	4 (3.2%) 	0 	5.7 (-0.6, 11.9) 	1.4 (-1.3, 4.0) 	
Cough 	3 (5.7%) 	1 (1.4%) 	4 (3.2%) 	0 	5.7 (-0.6, 11.9) 	1.4 (-1.3, 4.0) 	
 	 	 	 	 	 	 	
Reproductive system and breast disorders 	3 (5.7%) 	0 	3 (2.4%) 	1 (1.7%) 	4.0 (-3.1, 11.0) 	-1.7 (-5.0, 1.6) 	
Sexual Dysfunction 	2 (3.8%) 	0 	2 (1.6%) 	1 (1.7%) 	2.1 (-4.0, 8.2) 	-1.7 (-5.0, 1.6) 	
Abnormal Uterine Bleeding 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
Erectile Dysfunction 	1 (1.9%) 	0 	1 (0.8%) 	1 (1.7%) 	0.2 (-4.7, 5.1) 	-1.7 (-5.0, 1.6) 	
Excessive Menstrual Bleeding 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
 	 	 	 	 	 	 	
Ear and labyrinth disorders 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
Vertigo 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
 	 	 	 	 	 	 	
Endocrine disorders 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
Hyperglycemia 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
 	 	 	 	 	 	 	
Metabolism and nutrition disorders 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
Lipid Disorder 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
 	 	 	 	 	 	 	
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.