TSFAE11:	Subjects With Treatment-emergent Adverse Events With Frequency =[x]% in [Any Treatment Group] by System Organ Class and Preferred Term; Safety Analysis Set (Study jjcs - core)							
 	Active Study Agent 	Active Study Agent 	Active Study Agent 	 	Risk Difference (%) (95% CI) 	Risk Difference (%) (95% CI) 	
System Organ Class 	Xanomeline High Dose 	Xanomeline Low Dose 	Combined 	Placebo 	Xanomeline High Dose vs Placebo 	Xanomeline Low Dose vs Placebo 	
  Preferred Term, n (%) 	N=53 	N=73 	N=126 	N=59 	  	  	
General disorders and administration site conditions 	26 (49.1%) 	38 (52.1%) 	64 (50.8%) 	16 (27.1%) 	21.9 (4.3, 39.5) 	24.9 (8.8, 41.1) 	
APPLICATION SITE PRURITUS 	13 (24.5%) 	18 (24.7%) 	31 (24.6%) 	4 (6.8%) 	17.7 (4.5, 31.0) 	17.9 (6.1, 29.7) 	
APPLICATION SITE ERYTHEMA 	10 (18.9%) 	11 (15.1%) 	21 (16.7%) 	2 (3.4%) 	15.5 (4.0, 27.0) 	11.7 (2.3, 21.1) 	
APPLICATION SITE IRRITATION 	8 (15.1%) 	7 (9.6%) 	15 (11.9%) 	2 (3.4%) 	11.7 (1.0, 22.4) 	6.2 (-2.0, 14.4) 	
APPLICATION SITE DERMATITIS 	4 (7.5%) 	7 (9.6%) 	11 (8.7%) 	5 (8.5%) 	-0.9 (-11.0, 9.1) 	1.1 (-8.7, 10.9) 	
FATIGUE 	5 (9.4%) 	5 (6.8%) 	10 (7.9%) 	0 	9.4 (1.6, 17.3) 	6.8 (1.1, 12.6) 	
APPLICATION SITE VESICLES 	4 (7.5%) 	4 (5.5%) 	8 (6.3%) 	0 	7.5 (0.4, 14.7) 	5.5 (0.3, 10.7) 	
 	 	 	 	 	 	 	
Skin and subcutaneous tissue disorders 	34 (64.2%) 	28 (38.4%) 	62 (49.2%) 	16 (27.1%) 	37.0 (19.8, 54.2) 	11.2 (-4.7, 27.1) 	
PRURITUS 	20 (37.7%) 	14 (19.2%) 	34 (27.0%) 	6 (10.2%) 	27.6 (12.4, 42.7) 	9.0 (-2.9, 20.9) 	
ERYTHEMA 	12 (22.6%) 	8 (11.0%) 	20 (15.9%) 	6 (10.2%) 	12.5 (-1.2, 26.1) 	0.8 (-9.7, 11.3) 	
RASH 	5 (9.4%) 	9 (12.3%) 	14 (11.1%) 	4 (6.8%) 	2.7 (-7.5, 12.8) 	5.5 (-4.4, 15.5) 	
HYPERHIDROSIS 	8 (15.1%) 	4 (5.5%) 	12 (9.5%) 	2 (3.4%) 	11.7 (1.0, 22.4) 	2.1 (-4.9, 9.1) 	
SKIN IRRITATION 	4 (7.5%) 	4 (5.5%) 	8 (6.3%) 	3 (5.1%) 	2.5 (-6.6, 11.5) 	0.4 (-7.3, 8.1) 	
 	 	 	 	 	 	 	
Nervous system disorders 	18 (34.0%) 	18 (24.7%) 	36 (28.6%) 	5 (8.5%) 	25.5 (10.9, 40.1) 	16.2 (4.0, 28.4) 	
DIZZINESS 	8 (15.1%) 	8 (11.0%) 	16 (12.7%) 	0 	15.1 (5.5, 24.7) 	11.0 (3.8, 18.1) 	
HEADACHE 	5 (9.4%) 	3 (4.1%) 	8 (6.3%) 	2 (3.4%) 	6.0 (-3.1, 15.2) 	0.7 (-5.8, 7.2) 	
 	 	 	 	 	 	 	
Gastrointestinal disorders 	14 (26.4%) 	10 (13.7%) 	24 (19.0%) 	7 (11.9%) 	14.6 (0.1, 29.0) 	1.8 (-9.6, 13.2) 	
NAUSEA 	5 (9.4%) 	2 (2.7%) 	7 (5.6%) 	0 	9.4 (1.6, 17.3) 	2.7 (-1.0, 6.5) 	
VOMITING 	5 (9.4%) 	2 (2.7%) 	7 (5.6%) 	0 	9.4 (1.6, 17.3) 	2.7 (-1.0, 6.5) 	
DIARRHOEA 	2 (3.8%) 	3 (4.1%) 	5 (4.0%) 	3 (5.1%) 	-1.3 (-8.9, 6.3) 	-1.0 (-8.2, 6.2) 	
SALIVARY HYPERSECRETION 	4 (7.5%) 	0 	4 (3.2%) 	0 	7.5 (0.4, 14.7) 	0.0 (0.0, 0.0) 	
 	 	 	 	 	 	 	
Cardiac disorders 	11 (20.8%) 	11 (15.1%) 	22 (17.5%) 	7 (11.9%) 	8.9 (-4.8, 22.6) 	3.2 (-8.4, 14.8) 	
SINUS BRADYCARDIA 	7 (13.2%) 	4 (5.5%) 	11 (8.7%) 	0 	13.2 (4.1, 22.3) 	5.5 (0.3, 10.7) 	
MYOCARDIAL INFARCTION 	3 (5.7%) 	1 (1.4%) 	4 (3.2%) 	3 (5.1%) 	0.6 (-7.8, 8.9) 	-3.7 (-9.9, 2.5) 	
 	 	 	 	 	 	 	
Infections and infestations 	9 (17.0%) 	6 (8.2%) 	15 (11.9%) 	14 (23.7%) 	-6.7 (-21.6, 8.1) 	-15.5 (-28.1, -3.0) 	
NASOPHARYNGITIS 	3 (5.7%) 	3 (4.1%) 	6 (4.8%) 	2 (3.4%) 	2.3 (-5.5, 10.0) 	0.7 (-5.8, 7.2) 	
UPPER RESPIRATORY TRACT INFECTION 	2 (3.8%) 	0 	2 (1.6%) 	5 (8.5%) 	-4.7 (-13.5, 4.1) 	-8.5 (-15.6, -1.4) 	
 	 	 	 	 	 	 	
Respiratory, thoracic and mediastinal disorders 	7 (13.2%) 	6 (8.2%) 	13 (10.3%) 	5 (8.5%) 	4.7 (-6.8, 16.3) 	-0.3 (-9.8, 9.2) 	
COUGH 	3 (5.7%) 	4 (5.5%) 	7 (5.6%) 	1 (1.7%) 	4.0 (-3.1, 11.0) 	3.8 (-2.4, 10.0) 	
NASAL CONGESTION 	3 (5.7%) 	0 	3 (2.4%) 	2 (3.4%) 	2.3 (-5.5, 10.0) 	-3.4 (-8.0, 1.2) 	
 	 	 	 	 	 	 	
Investigations 	5 (9.4%) 	7 (9.6%) 	12 (9.5%) 	7 (11.9%) 	-2.4 (-13.8, 9.0) 	-2.3 (-12.9, 8.4) 	
ELECTROCARDIOGRAM ST SEGMENT DEPRESSION 	0 	1 (1.4%) 	1 (0.8%) 	3 (5.1%) 	-5.1 (-10.7, 0.5) 	-3.7 (-9.9, 2.5) 	

Note: Subjects are counted only once for any given event, regardless of the number of times they actually experienced the event. 	
Note: Subjects are counted only once for any given event, regardless of the number of times they actually experienced the event.	
Note: Subjects are counted only once for any given event, regardless of the number of times they actually experienced the event.	
Note: Subjects are counted only once for any given event, regardless of the number of times they actually experienced the event.	
Note: Subjects are counted only once for any given event, regardless of the number of times they actually experienced the event.	
Note: Subjects are counted only once for any given event, regardless of the number of times they actually experienced the event.	
Note: Subjects are counted only once for any given event, regardless of the number of times they actually experienced the event.	
Note: Adverse events are coded using MedDRA version 26.0. 	: Adverse events are coded using MedDRA version 26.	: Adverse events are coded using MedDRA version 26.	: Adverse events are coded using MedDRA version 26.	: Adverse events are coded using MedDRA version 26.	: Adverse events are coded using MedDRA version 26.	: Adverse events are coded using MedDRA version 26.