TSFAE05a:	Subjects With Treatment-emergent Related Adverse Events by System Organ Class, Preferred Term, and [Subgroup]; 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 	  	  	
Age Group: ≥18 to <65 years 	8 	5 	13 	7 	 	 	
 	  	  	  	  	  	  	
Subjects with ≥1 related AE 	2 (25.0%) 	1 (20.0%) 	3 (23.1%) 	1 (14.3%) 	10.7 (-28.9, 50.4) 	5.7 (-37.9, 49.3) 	
 	  	  	  	  	  	  	
General disorders and administration site conditions 	2 (25.0%) 	0 	2 (15.4%) 	0 	25.0 (-5.0, 55.0) 	0.0 (0.0, 0.0) 	
FATIGUE 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
MALAISE 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
 	 	 	 	 	 	 	
Cardiac disorders 	0 	1 (20.0%) 	1 (7.7%) 	0 	0.0 (0.0, 0.0) 	20.0 (-15.1, 55.1) 	
SINUS BRADYCARDIA 	0 	1 (20.0%) 	1 (7.7%) 	0 	0.0 (0.0, 0.0) 	20.0 (-15.1, 55.1) 	
 	 	 	 	 	 	 	
Injury, poisoning and procedural complications 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
CONTUSION 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
 	 	 	 	 	 	 	
Nervous system disorders 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
DIZZINESS 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
 	 	 	 	 	 	 	
Respiratory, thoracic and mediastinal disorders 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
EPISTAXIS 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
 	 	 	 	 	 	 	
Skin and subcutaneous tissue disorders 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
SKIN ODOUR ABNORMAL 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
 	 	 	 	 	 	 	
Infections and infestations 	0 	0 	0 	1 (14.3%) 	-14.3 (-40.2, 11.6) 	-14.3 (-40.2, 11.6) 	
CERVICITIS 	0 	0 	0 	1 (14.3%) 	-14.3 (-40.2, 11.6) 	-14.3 (-40.2, 11.6) 	
GASTROENTERITIS VIRAL 	0 	0 	0 	1 (14.3%) 	-14.3 (-40.2, 11.6) 	-14.3 (-40.2, 11.6) 	
URINARY TRACT INFECTION 	0 	0 	0 	1 (14.3%) 	-14.3 (-40.2, 11.6) 	-14.3 (-40.2, 11.6) 	
VAGINAL MYCOSIS 	0 	0 	0 	1 (14.3%) 	-14.3 (-40.2, 11.6) 	-14.3 (-40.2, 11.6) 	
 	 	 	 	 	 	 	
Renal and urinary disorders 	0 	0 	0 	1 (14.3%) 	-14.3 (-40.2, 11.6) 	-14.3 (-40.2, 11.6) 	
DYSURIA 	0 	0 	0 	1 (14.3%) 	-14.3 (-40.2, 11.6) 	-14.3 (-40.2, 11.6) 	
Age Group: ≥65 to <75 years 	16 	17 	33 	19 	 	 	
 	  	  	  	  	  	  	
Subjects with ≥1 related AE 	2 (12.5%) 	2 (11.8%) 	4 (12.1%) 	5 (26.3%) 	-13.8 (-39.4, 11.8) 	-14.6 (-39.6, 10.5) 	
 	  	  	  	  	  	  	
General disorders and administration site conditions 	1 (6.2%) 	2 (11.8%) 	3 (9.1%) 	0 	6.2 (-5.6, 18.1) 	11.8 (-3.6, 27.1) 	
CHEST PAIN 	1 (6.2%) 	0 	1 (3.0%) 	0 	6.2 (-5.6, 18.1) 	0.0 (0.0, 0.0) 	
FATIGUE 	0 	1 (5.9%) 	1 (3.0%) 	0 	0.0 (0.0, 0.0) 	5.9 (-5.3, 17.1) 	
PYREXIA 	0 	1 (5.9%) 	1 (3.0%) 	0 	0.0 (0.0, 0.0) 	5.9 (-5.3, 17.1) 	
 	 	 	 	 	 	 	
Respiratory, thoracic and mediastinal disorders 	1 (6.2%) 	1 (5.9%) 	2 (6.1%) 	1 (5.3%) 	1.0 (-14.6, 16.5) 	0.6 (-14.4, 15.6) 	
DYSPHONIA 	0 	1 (5.9%) 	1 (3.0%) 	0 	0.0 (0.0, 0.0) 	5.9 (-5.3, 17.1) 	
NASAL CONGESTION 	1 (6.2%) 	0 	1 (3.0%) 	0 	6.2 (-5.6, 18.1) 	0.0 (0.0, 0.0) 	
COUGH 	0 	0 	0 	1 (5.3%) 	-5.3 (-15.3, 4.8) 	-5.3 (-15.3, 4.8) 	
 	 	 	 	 	 	 	
Psychiatric disorders 	1 (6.2%) 	0 	1 (3.0%) 	1 (5.3%) 	1.0 (-14.6, 16.5) 	-5.3 (-15.3, 4.8) 	
NIGHTMARE 	1 (6.2%) 	0 	1 (3.0%) 	0 	6.2 (-5.6, 18.1) 	0.0 (0.0, 0.0) 	
DISORIENTATION 	0 	0 	0 	1 (5.3%) 	-5.3 (-15.3, 4.8) 	-5.3 (-15.3, 4.8) 	
 	 	 	 	 	 	 	
Eye disorders 	0 	0 	0 	1 (5.3%) 	-5.3 (-15.3, 4.8) 	-5.3 (-15.3, 4.8) 	
CONJUNCTIVITIS 	0 	0 	0 	1 (5.3%) 	-5.3 (-15.3, 4.8) 	-5.3 (-15.3, 4.8) 	
 	 	 	 	 	 	 	
Investigations 	0 	0 	0 	2 (10.5%) 	-10.5 (-24.3, 3.3) 	-10.5 (-24.3, 3.3) 	
ELECTROCARDIOGRAM ST SEGMENT DEPRESSION 	0 	0 	0 	1 (5.3%) 	-5.3 (-15.3, 4.8) 	-5.3 (-15.3, 4.8) 	
ELECTROCARDIOGRAM T WAVE AMPLITUDE DECREASED 	0 	0 	0 	1 (5.3%) 	-5.3 (-15.3, 4.8) 	-5.3 (-15.3, 4.8) 	
ELECTROCARDIOGRAM T WAVE INVERSION 	0 	0 	0 	1 (5.3%) 	-5.3 (-15.3, 4.8) 	-5.3 (-15.3, 4.8) 	
 	 	 	 	 	 	 	
Skin and subcutaneous tissue disorders 	0 	0 	0 	1 (5.3%) 	-5.3 (-15.3, 4.8) 	-5.3 (-15.3, 4.8) 	
RASH 	0 	0 	0 	1 (5.3%) 	-5.3 (-15.3, 4.8) 	-5.3 (-15.3, 4.8) 	
Age Group: ≥75 years 	29 	51 	80 	33 	 	 	
 	  	  	  	  	  	  	
Subjects with ≥1 related AE 	11 (37.9%) 	16 (31.4%) 	27 (33.8%) 	13 (39.4%) 	-1.5 (-25.7, 22.8) 	-8.0 (-29.0, 13.0) 	
 	  	  	  	  	  	  	
Nervous system disorders 	5 (17.2%) 	5 (9.8%) 	10 (12.5%) 	1 (3.0%) 	14.2 (-0.7, 29.2) 	6.8 (-3.3, 16.8) 	
DIZZINESS 	3 (10.3%) 	2 (3.9%) 	5 (6.2%) 	0 	10.3 (-0.7, 21.4) 	3.9 (-1.4, 9.2) 	
HEADACHE 	2 (6.9%) 	1 (2.0%) 	3 (3.8%) 	0 	6.9 (-2.3, 16.1) 	2.0 (-1.8, 5.8) 	
SOMNOLENCE 	1 (3.4%) 	1 (2.0%) 	2 (2.5%) 	0 	3.4 (-3.2, 10.1) 	2.0 (-1.8, 5.8) 	
TRANSIENT ISCHAEMIC ATTACK 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
PSYCHOMOTOR HYPERACTIVITY 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
 	 	 	 	 	 	 	
Gastrointestinal disorders 	4 (13.8%) 	2 (3.9%) 	6 (7.5%) 	2 (6.1%) 	7.7 (-7.2, 22.7) 	-2.1 (-11.9, 7.6) 	
DIARRHOEA 	1 (3.4%) 	1 (2.0%) 	2 (2.5%) 	1 (3.0%) 	0.4 (-8.4, 9.3) 	-1.1 (-8.0, 5.9) 	
NAUSEA 	2 (6.9%) 	0 	2 (2.5%) 	0 	6.9 (-2.3, 16.1) 	0.0 (0.0, 0.0) 	
VOMITING 	2 (6.9%) 	0 	2 (2.5%) 	0 	6.9 (-2.3, 16.1) 	0.0 (0.0, 0.0) 	
ABDOMINAL DISCOMFORT 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
ABDOMINAL PAIN 	0 	1 (2.0%) 	1 (1.2%) 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-1.1 (-8.0, 5.9) 	
CONSTIPATION 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
 	 	 	 	 	 	 	
General disorders and administration site conditions 	2 (6.9%) 	4 (7.8%) 	6 (7.5%) 	1 (3.0%) 	3.9 (-7.1, 14.8) 	4.8 (-4.6, 14.2) 	
FATIGUE 	0 	2 (3.9%) 	2 (2.5%) 	0 	0.0 (0.0, 0.0) 	3.9 (-1.4, 9.2) 	
ASTHENIA 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
CHEST PAIN 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
CHILLS 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
OEDEMA PERIPHERAL 	0 	1 (2.0%) 	1 (1.2%) 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-1.1 (-8.0, 5.9) 	
 	 	 	 	 	 	 	
Cardiac disorders 	2 (6.9%) 	2 (3.9%) 	4 (5.0%) 	3 (9.1%) 	-2.2 (-15.7, 11.3) 	-5.2 (-16.3, 6.0) 	
SINUS BRADYCARDIA 	2 (6.9%) 	0 	2 (2.5%) 	0 	6.9 (-2.3, 16.1) 	0.0 (0.0, 0.0) 	
PALPITATIONS 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
VENTRICULAR EXTRASYSTOLES 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
BUNDLE BRANCH BLOCK RIGHT 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
MYOCARDIAL INFARCTION 	0 	0 	0 	2 (6.1%) 	-6.1 (-14.2, 2.1) 	-6.1 (-14.2, 2.1) 	
SUPRAVENTRICULAR EXTRASYSTOLES 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
TACHYCARDIA 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
 	 	 	 	 	 	 	
Eye disorders 	0 	1 (2.0%) 	1 (1.2%) 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-1.1 (-8.0, 5.9) 	
CONJUNCTIVAL HAEMORRHAGE 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
EYE PRURITUS 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
 	 	 	 	 	 	 	
Injury, poisoning and procedural complications 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
CONTUSION 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
FALL 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
 	 	 	 	 	 	 	
Investigations 	0 	1 (2.0%) 	1 (1.2%) 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-1.1 (-8.0, 5.9) 	
ELECTROCARDIOGRAM T WAVE AMPLITUDE DECREASED 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
ELECTROCARDIOGRAM ST SEGMENT DEPRESSION 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
ELECTROCARDIOGRAM T WAVE INVERSION 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
 	 	 	 	 	 	 	
Metabolism and nutrition disorders 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
INCREASED APPETITE 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
 	 	 	 	 	 	 	
Musculoskeletal and connective tissue disorders 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
BACK PAIN 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
 	 	 	 	 	 	 	
Psychiatric disorders 	1 (3.4%) 	0 	1 (1.2%) 	4 (12.1%) 	-8.7 (-21.6, 4.3) 	-12.1 (-23.3, -1.0) 	
CONFUSIONAL STATE 	1 (3.4%) 	0 	1 (1.2%) 	1 (3.0%) 	0.4 (-8.4, 9.3) 	-3.0 (-8.9, 2.8) 	
AGITATION 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
DELUSION 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
DISTURBANCE IN SEXUAL AROUSAL 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
 	 	 	 	 	 	 	
Renal and urinary disorders 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
DYSURIA 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
 	 	 	 	 	 	 	
Respiratory, thoracic and mediastinal disorders 	0 	1 (2.0%) 	1 (1.2%) 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-1.1 (-8.0, 5.9) 	
COUGH 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
RHINORRHOEA 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
NASAL CONGESTION 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
 	 	 	 	 	 	 	
Endocrine disorders 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
BLEEDING ANOVULATORY 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
 	 	 	 	 	 	 	
Infections and infestations 	0 	0 	0 	3 (9.1%) 	-9.1 (-18.9, 0.7) 	-9.1 (-18.9, 0.7) 	
UPPER RESPIRATORY TRACT INFECTION 	0 	0 	0 	3 (9.1%) 	-9.1 (-18.9, 0.7) 	-9.1 (-18.9, 0.7) 	
 	 	 	 	 	 	 	
Skin and subcutaneous tissue disorders 	0 	0 	0 	3 (9.1%) 	-9.1 (-18.9, 0.7) 	-9.1 (-18.9, 0.7) 	
ALOPECIA 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
HYPERHIDROSIS 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
PRURITUS 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
 	 	 	 	 	 	 	
Vascular disorders 	0 	0 	0 	2 (6.1%) 	-6.1 (-14.2, 2.1) 	-6.1 (-14.2, 2.1) 	
HYPERTENSION 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
HYPOTENSION 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	

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.