TSFAE07b:	Subjects With Treatment-emergent Adverse Events of Special Interest - [AESI Grouping]; Safety Analysis Set (Study jjcs - core)							
 	Active Study Agent 	Active Study Agent 	Active Study Agent 	 	Risk Difference (%) (95% CI) 	Risk Difference (%) (95% CI) 	
 	Xanomeline High Dose 	Xanomeline Low Dose 	Combined 	Placebo 	Xanomeline High Dose vs Placebo 	Xanomeline Low Dose vs Placebo 	
AESI Assessment, n (%) 	N=53 	N=73 	N=126 	N=59 	  	  	
Seizure 	48 (90.6%) 	56 (76.7%) 	104 (82.5%) 	36 (61.0%) 	29.5 (14.8, 44.3) 	15.7 (-0.1, 31.5) 	
Preferred Term 	 	 	 	 	 	 	
ABNORMAL UTERINE BLEEDING 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
AGITATION 	0 	1 (1.4%) 	1 (0.8%) 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-0.3 (-4.6, 3.9) 	
APPLICATION SITE DERMATITIS 	2 (3.8%) 	0 	2 (1.6%) 	2 (3.4%) 	0.4 (-6.5, 7.3) 	-3.4 (-8.0, 1.2) 	
APPLICATION SITE DESQUAMATION 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
APPLICATION SITE ERYTHEMA 	3 (5.7%) 	3 (4.1%) 	6 (4.8%) 	0 	5.7 (-0.6, 11.9) 	4.1 (-0.4, 8.7) 	
APPLICATION SITE IRRITATION 	4 (7.5%) 	3 (4.1%) 	7 (5.6%) 	1 (1.7%) 	5.9 (-2.0, 13.7) 	2.4 (-3.2, 8.0) 	
APPLICATION SITE PRURITUS 	4 (7.5%) 	4 (5.5%) 	8 (6.3%) 	1 (1.7%) 	5.9 (-2.0, 13.7) 	3.8 (-2.4, 10.0) 	
APPLICATION SITE SWELLING 	1 (1.9%) 	1 (1.4%) 	2 (1.6%) 	0 	1.9 (-1.8, 5.5) 	1.4 (-1.3, 4.0) 	
APPLICATION SITE VESICLES 	0 	2 (2.7%) 	2 (1.6%) 	0 	0.0 (0.0, 0.0) 	2.7 (-1.0, 6.5) 	
ATRIAL FIBRILLATION 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
BACK PAIN 	1 (1.9%) 	0 	1 (0.8%) 	1 (1.7%) 	0.2 (-4.7, 5.1) 	-1.7 (-5.0, 1.6) 	
BLEEDING ANOVULATORY 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
BLISTER 	1 (1.9%) 	1 (1.4%) 	2 (1.6%) 	0 	1.9 (-1.8, 5.5) 	1.4 (-1.3, 4.0) 	
BLOOD GLUCOSE INCREASED 	1 (1.9%) 	1 (1.4%) 	2 (1.6%) 	0 	1.9 (-1.8, 5.5) 	1.4 (-1.3, 4.0) 	
CHEST DISCOMFORT 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
CHEST PAIN 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
COLON CANCER 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
COMPLEX PARTIAL SEIZURES 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
CONFUSIONAL STATE 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
DECREASED APPETITE 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
DELUSION 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
DEPRESSED MOOD 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
DIARRHOEA 	0 	1 (1.4%) 	1 (0.8%) 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-0.3 (-4.6, 3.9) 	
DISTURBANCE IN SEXUAL AROUSAL 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
DIZZINESS 	2 (3.8%) 	2 (2.7%) 	4 (3.2%) 	0 	3.8 (-1.4, 8.9) 	2.7 (-1.0, 6.5) 	
DYSPEPSIA 	0 	1 (1.4%) 	1 (0.8%) 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-0.3 (-4.6, 3.9) 	
DYSURIA 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
EAR INFECTION 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
ELECTROCARDIOGRAM ST SEGMENT DEPRESSION 	0 	0 	0 	2 (3.4%) 	-3.4 (-8.0, 1.2) 	-3.4 (-8.0, 1.2) 	
ELECTROCARDIOGRAM T WAVE INVERSION 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
ERECTILE DYSFUNCTION 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
ERYTHEMA 	4 (7.5%) 	3 (4.1%) 	7 (5.6%) 	2 (3.4%) 	4.2 (-4.3, 12.6) 	0.7 (-5.8, 7.2) 	
EYE LASER SURGERY 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
EYE PRURITUS 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
FALL 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
FATIGUE 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
HEMIANOPIA HOMONYMOUS 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
HYPERHIDROSIS 	1 (1.9%) 	1 (1.4%) 	2 (1.6%) 	1 (1.7%) 	0.2 (-4.7, 5.1) 	-0.3 (-4.6, 3.9) 	
HYPOTENSION 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
INFLUENZA 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
LOWER RESPIRATORY TRACT INFECTION 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
MYOCARDIAL INFARCTION 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
NASOPHARYNGITIS 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
NAUSEA 	2 (3.8%) 	1 (1.4%) 	3 (2.4%) 	0 	3.8 (-1.4, 8.9) 	1.4 (-1.3, 4.0) 	
PALPITATIONS 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
PARKINSON'S DISEASE 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
PRURITUS 	7 (13.2%) 	5 (6.8%) 	12 (9.5%) 	2 (3.4%) 	9.8 (-0.4, 20.0) 	3.5 (-3.9, 10.9) 	
PSYCHOMOTOR HYPERACTIVITY 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
RASH 	0 	2 (2.7%) 	2 (1.6%) 	3 (5.1%) 	-5.1 (-10.7, 0.5) 	-2.3 (-9.1, 4.4) 	
RASH PRURITIC 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
SECRETION DISCHARGE 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
SINUS ARRHYTHMIA 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
SINUS BRADYCARDIA 	4 (7.5%) 	0 	4 (3.2%) 	0 	7.5 (0.4, 14.7) 	0.0 (0.0, 0.0) 	
SKIN IRRITATION 	0 	3 (4.1%) 	3 (2.4%) 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	2.4 (-3.2, 8.0) 	
SKIN LACERATION 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
SKIN ULCER 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
SUPRAVENTRICULAR TACHYCARDIA 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
SYNCOPE 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
TRANSIENT ISCHAEMIC ATTACK 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
ULCER 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
UPPER RESPIRATORY TRACT INFECTION 	1 (1.9%) 	0 	1 (0.8%) 	3 (5.1%) 	-3.2 (-9.9, 3.5) 	-5.1 (-10.7, 0.5) 	
URTICARIA 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
VENTRICULAR EXTRASYSTOLES 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
VENTRICULAR SEPTAL DEFECT 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
VISION BLURRED 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
VOMITING 	2 (3.8%) 	0 	2 (1.6%) 	0 	3.8 (-1.4, 8.9) 	0.0 (0.0, 0.0) 	
 	 	 	 	 	 	 	
Maximum toxicity 	 	 	 	 	 	 	
Grade 5 	17 (32.1%) 	19 (26.0%) 	36 (28.6%) 	17 (28.8%) 	3.3 (-13.8, 20.3) 	-2.8 (-18.1, 12.5) 	
Grade 4 	9 (17.0%) 	15 (20.5%) 	24 (19.0%) 	3 (5.1%) 	11.9 (0.3, 23.5) 	15.5 (4.6, 26.3) 	
Grade 3 	11 (20.8%) 	10 (13.7%) 	21 (16.7%) 	7 (11.9%) 	8.9 (-4.8, 22.6) 	1.8 (-9.6, 13.2) 	
Grade 2 	7 (13.2%) 	8 (11.0%) 	15 (11.9%) 	3 (5.1%) 	8.1 (-2.6, 18.8) 	5.9 (-3.2, 15.0) 	
Grade 1 	2 (3.8%) 	2 (2.7%) 	4 (3.2%) 	3 (5.1%) 	-1.3 (-8.9, 6.3) 	-2.3 (-9.1, 4.4) 	
 	 	 	 	 	 	 	
Serious 	26 (49.1%) 	27 (37.0%) 	53 (42.1%) 	19 (32.2%) 	16.9 (-1.1, 34.8) 	4.8 (-11.5, 21.1) 	
Deaths 	0 	0 	0 	0 	0.0 (0.0, 0.0) 	0.0 (0.0, 0.0) 	
 	 	 	 	 	 	 	
Resulting in treatment discontinuation 	3 (5.7%) 	5 (6.8%) 	8 (6.3%) 	6 (10.2%) 	-4.5 (-14.4, 5.4) 	-3.3 (-13.0, 6.3) 	
 	 	 	 	 	 	 	
Relateda 	4 (7.5%) 	5 (6.8%) 	9 (7.1%) 	9 (15.3%) 	-7.7 (-19.3, 3.9) 	-8.4 (-19.3, 2.4) 	
 	 	 	 	 	 	 	
Laboratory assessmentb 	52 (98.1%) 	63 (86.3%) 	115 (91.3%) 	58 (98.3%) 	-0.2 (-5.1, 4.7) 	-12.0 (-20.6, -3.5) 	
AST>5xULN 	49 (92.5%) 	54 (74.0%) 	103 (81.7%) 	55 (93.2%) 	-0.8 (-10.3, 8.8) 	-19.2 (-31.2, -7.3) 	
ALT>5xULN 	51 (96.2%) 	51 (69.9%) 	102 (81.0%) 	47 (79.7%) 	16.6 (5.1, 28.0) 	-9.8 (-24.5, 4.9) 	

a As determined by investigator. 	
a As determined by investigator.	
a As determined by investigator.	
a As determined by investigator.	
a As determined by investigator.	
a As determined by investigator.	
a As determined by investigator.	
b Relevant laboratory results for AESI evaluation. 	b Relevant laboratory results for AESI evaluation.	b Relevant laboratory results for AESI evaluation.	b Relevant laboratory results for AESI evaluation.	b Relevant laboratory results for AESI evaluation.	b Relevant laboratory results for AESI evaluation.	b Relevant laboratory results for AESI evaluation.	
Note: Subjects are counted only once for any given event, regardless of the number of times they actually experienced the event. 	: Subjects are counted only once for any given event, regardless of the number of times they actually experienced the event.	: Subjects are counted only once for any given event, regardless of the number of times they actually experienced the event.	: Subjects are counted only once for any given event, regardless of the number of times they actually experienced the event.	: Subjects are counted only once for any given event, regardless of the number of times they actually experienced the event.	: Subjects are counted only once for any given event, regardless of the number of times they actually experienced the event.	: 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; toxicity grade is evaluated according to NCI-CTCAE version 5.0.. 	: Adverse events are coded using MedDRA version 26; toxicity grade is evaluated according to NCI-CTCAE version 5..	: Adverse events are coded using MedDRA version 26; toxicity grade is evaluated according to NCI-CTCAE version 5..	: Adverse events are coded using MedDRA version 26; toxicity grade is evaluated according to NCI-CTCAE version 5..	: Adverse events are coded using MedDRA version 26; toxicity grade is evaluated according to NCI-CTCAE version 5..	: Adverse events are coded using MedDRA version 26; toxicity grade is evaluated according to NCI-CTCAE version 5..	: Adverse events are coded using MedDRA version 26; toxicity grade is evaluated according to NCI-CTCAE version 5..