TSFAE07a:	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 	 	 	 	 	 	 	
ABDOMINAL PAIN 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
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 BLEEDING 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
APPLICATION SITE DERMATITIS 	2 (3.8%) 	1 (1.4%) 	3 (2.4%) 	3 (5.1%) 	-1.3 (-8.9, 6.3) 	-3.7 (-9.9, 2.5) 	
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 	6 (11.3%) 	5 (6.8%) 	11 (8.7%) 	0 	11.3 (2.8, 19.9) 	6.8 (1.1, 12.6) 	
APPLICATION SITE INDURATION 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
APPLICATION SITE IRRITATION 	3 (5.7%) 	2 (2.7%) 	5 (4.0%) 	2 (3.4%) 	2.3 (-5.5, 10.0) 	-0.7 (-6.6, 5.3) 	
APPLICATION SITE PRURITUS 	2 (3.8%) 	5 (6.8%) 	7 (5.6%) 	1 (1.7%) 	2.1 (-4.0, 8.2) 	5.2 (-1.5, 11.8) 	
APPLICATION SITE REACTION 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
APPLICATION SITE SWELLING 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
APPLICATION SITE VESICLES 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
ARTHRALGIA 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
ATRIAL FIBRILLATION 	0 	2 (2.7%) 	2 (1.6%) 	0 	0.0 (0.0, 0.0) 	2.7 (-1.0, 6.5) 	
BACK PAIN 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
BLEEDING ANOVULATORY 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
BLISTER 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
BLOOD CREATINE PHOSPHOKINASE INCREASED 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
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) 	
BUNDLE BRANCH BLOCK RIGHT 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
CARDIAC DISORDER 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
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) 	
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 	0 	2 (2.7%) 	2 (1.6%) 	0 	0.0 (0.0, 0.0) 	2.7 (-1.0, 6.5) 	
DYSPEPSIA 	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 	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 	5 (9.4%) 	2 (2.7%) 	7 (5.6%) 	4 (6.8%) 	2.7 (-7.5, 12.8) 	-4.0 (-11.5, 3.4) 	
EXCORIATION 	1 (1.9%) 	1 (1.4%) 	2 (1.6%) 	0 	1.9 (-1.8, 5.5) 	1.4 (-1.3, 4.0) 	
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) 	
FATIGUE 	0 	2 (2.7%) 	2 (1.6%) 	0 	0.0 (0.0, 0.0) 	2.7 (-1.0, 6.5) 	
GASTROENTERITIS VIRAL 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
GLOSSITIS 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
HEADACHE 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
HIP FRACTURE 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
HYPERHIDROSIS 	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) 	
LETHARGY 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
LOCALISED INFECTION 	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) 	
MALAISE 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
MUSCLE SPASMS 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
MYOCARDIAL INFARCTION 	2 (3.8%) 	0 	2 (1.6%) 	2 (3.4%) 	0.4 (-6.5, 7.3) 	-3.4 (-8.0, 1.2) 	
NASOPHARYNGITIS 	1 (1.9%) 	1 (1.4%) 	2 (1.6%) 	0 	1.9 (-1.8, 5.5) 	1.4 (-1.3, 4.0) 	
NAUSEA 	1 (1.9%) 	1 (1.4%) 	2 (1.6%) 	0 	1.9 (-1.8, 5.5) 	1.4 (-1.3, 4.0) 	
OEDEMA 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
PALPITATIONS 	0 	2 (2.7%) 	2 (1.6%) 	0 	0.0 (0.0, 0.0) 	2.7 (-1.0, 6.5) 	
PARKINSON'S DISEASE 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
PARTIAL SEIZURES WITH SECONDARY GENERALISATION 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
PRURITUS 	4 (7.5%) 	3 (4.1%) 	7 (5.6%) 	1 (1.7%) 	5.9 (-2.0, 13.7) 	2.4 (-3.2, 8.0) 	
RASH 	0 	2 (2.7%) 	2 (1.6%) 	0 	0.0 (0.0, 0.0) 	2.7 (-1.0, 6.5) 	
SHOULDER PAIN 	0 	0 	0 	1 (1.7%) 	-1.7 (-5.0, 1.6) 	-1.7 (-5.0, 1.6) 	
SINUS BRADYCARDIA 	4 (7.5%) 	1 (1.4%) 	5 (4.0%) 	0 	7.5 (0.4, 14.7) 	1.4 (-1.3, 4.0) 	
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) 	
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) 	
UPPER RESPIRATORY TRACT INFECTION 	0 	0 	0 	2 (3.4%) 	-3.4 (-8.0, 1.2) 	-3.4 (-8.0, 1.2) 	
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 	1 (1.9%) 	0 	1 (0.8%) 	0 	1.9 (-1.8, 5.5) 	0.0 (0.0, 0.0) 	
VOMITING 	2 (3.8%) 	0 	2 (1.6%) 	0 	3.8 (-1.4, 8.9) 	0.0 (0.0, 0.0) 	
WEIGHT DECREASED 	0 	1 (1.4%) 	1 (0.8%) 	0 	0.0 (0.0, 0.0) 	1.4 (-1.3, 4.0) 	
 	 	 	 	 	 	 	
Maximum severity 	 	 	 	 	 	 	
Severe 	1 (1.9%) 	6 (8.2%) 	7 (5.6%) 	1 (1.7%) 	0.2 (-4.7, 5.1) 	6.5 (-0.6, 13.6) 	
Moderate 	26 (49.1%) 	31 (42.5%) 	57 (45.2%) 	10 (16.9%) 	32.1 (15.6, 48.6) 	25.5 (10.7, 40.4) 	
Mild 	21 (39.6%) 	19 (26.0%) 	40 (31.7%) 	25 (42.4%) 	-2.8 (-21.0, 15.5) 	-16.3 (-32.5, -0.2) 	
 	 	 	 	 	 	 	
Serious 	24 (45.3%) 	27 (37.0%) 	51 (40.5%) 	23 (39.0%) 	6.3 (-12.0, 24.6) 	-2.0 (-18.7, 14.7) 	
Deaths 	0 	0 	0 	0 	0.0 (0.0, 0.0) 	0.0 (0.0, 0.0) 	
 	 	 	 	 	 	 	
Resulting in treatment discontinuation 	3 (5.7%) 	6 (8.2%) 	9 (7.1%) 	8 (13.6%) 	-7.9 (-18.6, 2.8) 	-5.3 (-16.1, 5.4) 	
 	 	 	 	 	 	 	
Relateda 	5 (9.4%) 	6 (8.2%) 	11 (8.7%) 	8 (13.6%) 	-4.1 (-15.9, 7.6) 	-5.3 (-16.1, 5.4) 	
 	 	 	 	 	 	 	
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. 	: 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.