TSFAE02a:	Subjects With Treatment-emergent 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 AE 	8 (100.0%) 	5 (100.0%) 	13 (100.0%) 	3 (42.9%) 	57.1 (20.5, 93.8) 	57.1 (20.5, 93.8) 	
 	  	  	  	  	  	  	
General disorders and administration site conditions 	6 (75.0%) 	4 (80.0%) 	10 (76.9%) 	2 (28.6%) 	46.4 (1.5, 91.4) 	51.4 (3.0, 99.9) 	
APPLICATION SITE PRURITUS 	4 (50.0%) 	3 (60.0%) 	7 (53.8%) 	1 (14.3%) 	35.7 (-7.6, 79.0) 	45.7 (-4.4, 95.9) 	
APPLICATION SITE ERYTHEMA 	5 (62.5%) 	1 (20.0%) 	6 (46.2%) 	0 	62.5 (29.0, 96.0) 	20.0 (-15.1, 55.1) 	
APPLICATION SITE IRRITATION 	2 (25.0%) 	1 (20.0%) 	3 (23.1%) 	1 (14.3%) 	10.7 (-28.9, 50.4) 	5.7 (-37.9, 49.3) 	
APPLICATION SITE SWELLING 	1 (12.5%) 	1 (20.0%) 	2 (15.4%) 	0 	12.5 (-10.4, 35.4) 	20.0 (-15.1, 55.1) 	
APPLICATION SITE VESICLES 	1 (12.5%) 	1 (20.0%) 	2 (15.4%) 	0 	12.5 (-10.4, 35.4) 	20.0 (-15.1, 55.1) 	
APPLICATION SITE PERSPIRATION 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	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) 	
FEELING ABNORMAL 	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) 	
PAIN 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
ASTHENIA 	0 	0 	0 	1 (14.3%) 	-14.3 (-40.2, 11.6) 	-14.3 (-40.2, 11.6) 	
 	 	 	 	 	 	 	
Skin and subcutaneous tissue disorders 	6 (75.0%) 	1 (20.0%) 	7 (53.8%) 	2 (28.6%) 	46.4 (1.5, 91.4) 	-8.6 (-57.0, 39.9) 	
PRURITUS 	4 (50.0%) 	1 (20.0%) 	5 (38.5%) 	0 	50.0 (15.4, 84.6) 	20.0 (-15.1, 55.1) 	
ERYTHEMA 	3 (37.5%) 	1 (20.0%) 	4 (30.8%) 	1 (14.3%) 	23.2 (-19.2, 65.6) 	5.7 (-37.9, 49.3) 	
ACTINIC KERATOSIS 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
HYPERHIDROSIS 	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) 	
DRUG ERUPTION 	0 	0 	0 	1 (14.3%) 	-14.3 (-40.2, 11.6) 	-14.3 (-40.2, 11.6) 	
RASH 	0 	0 	0 	1 (14.3%) 	-14.3 (-40.2, 11.6) 	-14.3 (-40.2, 11.6) 	
 	 	 	 	 	 	 	
Gastrointestinal disorders 	4 (50.0%) 	0 	4 (30.8%) 	1 (14.3%) 	35.7 (-7.6, 79.0) 	-14.3 (-40.2, 11.6) 	
SALIVARY HYPERSECRETION 	3 (37.5%) 	0 	3 (23.1%) 	0 	37.5 (4.0, 71.0) 	0.0 (0.0, 0.0) 	
NAUSEA 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
STOMACH DISCOMFORT 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
VOMITING 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
DYSPEPSIA 	0 	0 	0 	1 (14.3%) 	-14.3 (-40.2, 11.6) 	-14.3 (-40.2, 11.6) 	
GASTROOESOPHAGEAL REFLUX DISEASE 	0 	0 	0 	1 (14.3%) 	-14.3 (-40.2, 11.6) 	-14.3 (-40.2, 11.6) 	
 	 	 	 	 	 	 	
Respiratory, thoracic and mediastinal disorders 	4 (50.0%) 	0 	4 (30.8%) 	0 	50.0 (15.4, 84.6) 	0.0 (0.0, 0.0) 	
EPISTAXIS 	2 (25.0%) 	0 	2 (15.4%) 	0 	25.0 (-5.0, 55.0) 	0.0 (0.0, 0.0) 	
NASAL CONGESTION 	2 (25.0%) 	0 	2 (15.4%) 	0 	25.0 (-5.0, 55.0) 	0.0 (0.0, 0.0) 	
COUGH 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
PHARYNGOLARYNGEAL PAIN 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
PRODUCTIVE COUGH 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
RESPIRATORY TRACT CONGESTION 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
RHINORRHOEA 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
 	 	 	 	 	 	 	
Infections and infestations 	3 (37.5%) 	0 	3 (23.1%) 	1 (14.3%) 	23.2 (-19.2, 65.6) 	-14.3 (-40.2, 11.6) 	
HORDEOLUM 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
LOWER RESPIRATORY TRACT INFECTION 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
RHINITIS 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
UPPER RESPIRATORY TRACT INFECTION 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
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) 	
 	 	 	 	 	 	 	
Nervous system disorders 	3 (37.5%) 	0 	3 (23.1%) 	0 	37.5 (4.0, 71.0) 	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) 	
HEADACHE 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
PARAESTHESIA 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
PAROSMIA 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
 	 	 	 	 	 	 	
Musculoskeletal and connective tissue disorders 	2 (25.0%) 	0 	2 (15.4%) 	0 	25.0 (-5.0, 55.0) 	0.0 (0.0, 0.0) 	
FLANK PAIN 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
MYALGIA 	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%) 	1 (14.3%) 	-14.3 (-40.2, 11.6) 	5.7 (-37.9, 49.3) 	
SINUS BRADYCARDIA 	0 	1 (20.0%) 	1 (7.7%) 	0 	0.0 (0.0, 0.0) 	20.0 (-15.1, 55.1) 	
ATRIOVENTRICULAR BLOCK SECOND DEGREE 	0 	0 	0 	1 (14.3%) 	-14.3 (-40.2, 11.6) 	-14.3 (-40.2, 11.6) 	
 	 	 	 	 	 	 	
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) 	
 	 	 	 	 	 	 	
Psychiatric disorders 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
LIBIDO DECREASED 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
LISTLESS 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
 	 	 	 	 	 	 	
Renal and urinary disorders 	1 (12.5%) 	0 	1 (7.7%) 	1 (14.3%) 	-1.8 (-36.4, 32.8) 	-14.3 (-40.2, 11.6) 	
CALCULUS URETHRAL 	1 (12.5%) 	0 	1 (7.7%) 	0 	12.5 (-10.4, 35.4) 	0.0 (0.0, 0.0) 	
DYSURIA 	0 	0 	0 	1 (14.3%) 	-14.3 (-40.2, 11.6) 	-14.3 (-40.2, 11.6) 	
 	 	 	 	 	 	 	
Reproductive system and breast disorders 	0 	0 	0 	2 (28.6%) 	-28.6 (-62.0, 4.9) 	-28.6 (-62.0, 4.9) 	
ERECTILE DYSFUNCTION 	0 	0 	0 	1 (14.3%) 	-14.3 (-40.2, 11.6) 	-14.3 (-40.2, 11.6) 	
PELVIC PAIN 	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 AE 	14 (87.5%) 	15 (88.2%) 	29 (87.9%) 	13 (68.4%) 	19.1 (-7.4, 45.5) 	19.8 (-6.1, 45.7) 	
 	  	  	  	  	  	  	
General disorders and administration site conditions 	7 (43.8%) 	10 (58.8%) 	17 (51.5%) 	6 (31.6%) 	12.2 (-19.9, 44.2) 	27.2 (-4.1, 58.6) 	
APPLICATION SITE PRURITUS 	5 (31.2%) 	5 (29.4%) 	10 (30.3%) 	0 	31.2 (8.5, 54.0) 	29.4 (7.8, 51.1) 	
APPLICATION SITE ERYTHEMA 	2 (12.5%) 	3 (17.6%) 	5 (15.2%) 	2 (10.5%) 	2.0 (-19.3, 23.3) 	7.1 (-15.7, 29.9) 	
APPLICATION SITE IRRITATION 	2 (12.5%) 	2 (11.8%) 	4 (12.1%) 	0 	12.5 (-3.7, 28.7) 	11.8 (-3.6, 27.1) 	
APPLICATION SITE VESICLES 	1 (6.2%) 	2 (11.8%) 	3 (9.1%) 	0 	6.2 (-5.6, 18.1) 	11.8 (-3.6, 27.1) 	
APPLICATION SITE DERMATITIS 	1 (6.2%) 	1 (5.9%) 	2 (6.1%) 	3 (15.8%) 	-9.5 (-29.8, 10.7) 	-9.9 (-29.8, 9.9) 	
APPLICATION SITE URTICARIA 	0 	2 (11.8%) 	2 (6.1%) 	0 	0.0 (0.0, 0.0) 	11.8 (-3.6, 27.1) 	
CHEST DISCOMFORT 	1 (6.2%) 	1 (5.9%) 	2 (6.1%) 	0 	6.2 (-5.6, 18.1) 	5.9 (-5.3, 17.1) 	
FATIGUE 	1 (6.2%) 	1 (5.9%) 	2 (6.1%) 	0 	6.2 (-5.6, 18.1) 	5.9 (-5.3, 17.1) 	
APPLICATION SITE PAIN 	1 (6.2%) 	0 	1 (3.0%) 	0 	6.2 (-5.6, 18.1) 	0.0 (0.0, 0.0) 	
CHEST PAIN 	1 (6.2%) 	0 	1 (3.0%) 	0 	6.2 (-5.6, 18.1) 	0.0 (0.0, 0.0) 	
FEELING COLD 	1 (6.2%) 	0 	1 (3.0%) 	0 	6.2 (-5.6, 18.1) 	0.0 (0.0, 0.0) 	
PYREXIA 	0 	1 (5.9%) 	1 (3.0%) 	0 	0.0 (0.0, 0.0) 	5.9 (-5.3, 17.1) 	
OEDEMA PERIPHERAL 	0 	0 	0 	1 (5.3%) 	-5.3 (-15.3, 4.8) 	-5.3 (-15.3, 4.8) 	
 	 	 	 	 	 	 	
Skin and subcutaneous tissue disorders 	9 (56.2%) 	6 (35.3%) 	15 (45.5%) 	4 (21.1%) 	35.2 (4.8, 65.6) 	14.2 (-14.9, 43.4) 	
PRURITUS 	6 (37.5%) 	3 (17.6%) 	9 (27.3%) 	1 (5.3%) 	32.2 (6.5, 58.0) 	12.4 (-8.3, 33.1) 	
ERYTHEMA 	2 (12.5%) 	2 (11.8%) 	4 (12.1%) 	1 (5.3%) 	7.2 (-11.8, 26.3) 	6.5 (-11.8, 24.8) 	
HYPERHIDROSIS 	2 (12.5%) 	1 (5.9%) 	3 (9.1%) 	1 (5.3%) 	7.2 (-11.8, 26.3) 	0.6 (-14.4, 15.6) 	
RASH 	1 (6.2%) 	2 (11.8%) 	3 (9.1%) 	2 (10.5%) 	-4.3 (-22.5, 13.9) 	1.2 (-19.4, 21.9) 	
RASH ERYTHEMATOUS 	0 	1 (5.9%) 	1 (3.0%) 	0 	0.0 (0.0, 0.0) 	5.9 (-5.3, 17.1) 	
RASH MACULO-PAPULAR 	1 (6.2%) 	0 	1 (3.0%) 	0 	6.2 (-5.6, 18.1) 	0.0 (0.0, 0.0) 	
RASH PRURITIC 	1 (6.2%) 	0 	1 (3.0%) 	0 	6.2 (-5.6, 18.1) 	0.0 (0.0, 0.0) 	
SKIN IRRITATION 	1 (6.2%) 	0 	1 (3.0%) 	0 	6.2 (-5.6, 18.1) 	0.0 (0.0, 0.0) 	
URTICARIA 	0 	1 (5.9%) 	1 (3.0%) 	0 	0.0 (0.0, 0.0) 	5.9 (-5.3, 17.1) 	
 	 	 	 	 	 	 	
Nervous system disorders 	5 (31.2%) 	4 (23.5%) 	9 (27.3%) 	3 (15.8%) 	15.5 (-12.6, 43.5) 	7.7 (-18.2, 33.7) 	
DIZZINESS 	2 (12.5%) 	4 (23.5%) 	6 (18.2%) 	0 	12.5 (-3.7, 28.7) 	23.5 (3.4, 43.7) 	
HEADACHE 	1 (6.2%) 	1 (5.9%) 	2 (6.1%) 	2 (10.5%) 	-4.3 (-22.5, 13.9) 	-4.6 (-22.4, 13.1) 	
COGNITIVE DISORDER 	1 (6.2%) 	0 	1 (3.0%) 	0 	6.2 (-5.6, 18.1) 	0.0 (0.0, 0.0) 	
PARTIAL SEIZURES WITH SECONDARY GENERALISATION 	1 (6.2%) 	0 	1 (3.0%) 	0 	6.2 (-5.6, 18.1) 	0.0 (0.0, 0.0) 	
STUPOR 	0 	1 (5.9%) 	1 (3.0%) 	0 	0.0 (0.0, 0.0) 	5.9 (-5.3, 17.1) 	
TRANSIENT ISCHAEMIC ATTACK 	0 	1 (5.9%) 	1 (3.0%) 	0 	0.0 (0.0, 0.0) 	5.9 (-5.3, 17.1) 	
PARKINSON'S DISEASE 	0 	0 	0 	1 (5.3%) 	-5.3 (-15.3, 4.8) 	-5.3 (-15.3, 4.8) 	
 	 	 	 	 	 	 	
Investigations 	4 (25.0%) 	1 (5.9%) 	5 (15.2%) 	3 (15.8%) 	9.2 (-17.6, 36.0) 	-9.9 (-29.8, 9.9) 	
BIOPSY 	1 (6.2%) 	0 	1 (3.0%) 	0 	6.2 (-5.6, 18.1) 	0.0 (0.0, 0.0) 	
BIOPSY PROSTATE 	1 (6.2%) 	0 	1 (3.0%) 	0 	6.2 (-5.6, 18.1) 	0.0 (0.0, 0.0) 	
BLOOD CHOLESTEROL INCREASED 	1 (6.2%) 	0 	1 (3.0%) 	0 	6.2 (-5.6, 18.1) 	0.0 (0.0, 0.0) 	
ELECTROCARDIOGRAM T WAVE INVERSION 	1 (6.2%) 	0 	1 (3.0%) 	1 (5.3%) 	1.0 (-14.6, 16.5) 	-5.3 (-15.3, 4.8) 	
WEIGHT DECREASED 	0 	1 (5.9%) 	1 (3.0%) 	0 	0.0 (0.0, 0.0) 	5.9 (-5.3, 17.1) 	
BLOOD CREATINE PHOSPHOKINASE INCREASED 	0 	0 	0 	1 (5.3%) 	-5.3 (-15.3, 4.8) 	-5.3 (-15.3, 4.8) 	
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) 	
 	 	 	 	 	 	 	
Psychiatric disorders 	2 (12.5%) 	3 (17.6%) 	5 (15.2%) 	2 (10.5%) 	2.0 (-19.3, 23.3) 	7.1 (-15.7, 29.9) 	
CONFUSIONAL STATE 	0 	2 (11.8%) 	2 (6.1%) 	1 (5.3%) 	-5.3 (-15.3, 4.8) 	6.5 (-11.8, 24.8) 	
DEPRESSED MOOD 	0 	1 (5.9%) 	1 (3.0%) 	0 	0.0 (0.0, 0.0) 	5.9 (-5.3, 17.1) 	
HALLUCINATION, VISUAL 	1 (6.2%) 	0 	1 (3.0%) 	0 	6.2 (-5.6, 18.1) 	0.0 (0.0, 0.0) 	
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) 	
 	 	 	 	 	 	 	
Gastrointestinal disorders 	2 (12.5%) 	2 (11.8%) 	4 (12.1%) 	2 (10.5%) 	2.0 (-19.3, 23.3) 	1.2 (-19.4, 21.9) 	
NAUSEA 	1 (6.2%) 	1 (5.9%) 	2 (6.1%) 	0 	6.2 (-5.6, 18.1) 	5.9 (-5.3, 17.1) 	
VOMITING 	1 (6.2%) 	1 (5.9%) 	2 (6.1%) 	0 	6.2 (-5.6, 18.1) 	5.9 (-5.3, 17.1) 	
DIARRHOEA 	0 	1 (5.9%) 	1 (3.0%) 	1 (5.3%) 	-5.3 (-15.3, 4.8) 	0.6 (-14.4, 15.6) 	
GLOSSITIS 	0 	0 	0 	1 (5.3%) 	-5.3 (-15.3, 4.8) 	-5.3 (-15.3, 4.8) 	
 	 	 	 	 	 	 	
Respiratory, thoracic and mediastinal disorders 	2 (12.5%) 	1 (5.9%) 	3 (9.1%) 	2 (10.5%) 	2.0 (-19.3, 23.3) 	-4.6 (-22.4, 13.1) 	
ALLERGIC GRANULOMATOUS ANGIITIS 	1 (6.2%) 	0 	1 (3.0%) 	0 	6.2 (-5.6, 18.1) 	0.0 (0.0, 0.0) 	
COUGH 	1 (6.2%) 	0 	1 (3.0%) 	1 (5.3%) 	1.0 (-14.6, 16.5) 	-5.3 (-15.3, 4.8) 	
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) 	
POSTNASAL DRIP 	0 	0 	0 	1 (5.3%) 	-5.3 (-15.3, 4.8) 	-5.3 (-15.3, 4.8) 	
 	 	 	 	 	 	 	
Cardiac 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) 	
SINUS BRADYCARDIA 	1 (6.2%) 	1 (5.9%) 	2 (6.1%) 	0 	6.2 (-5.6, 18.1) 	5.9 (-5.3, 17.1) 	
PALPITATIONS 	0 	1 (5.9%) 	1 (3.0%) 	0 	0.0 (0.0, 0.0) 	5.9 (-5.3, 17.1) 	
SINUS ARRHYTHMIA 	0 	0 	0 	1 (5.3%) 	-5.3 (-15.3, 4.8) 	-5.3 (-15.3, 4.8) 	
 	 	 	 	 	 	 	
Injury, poisoning and procedural complications 	1 (6.2%) 	1 (5.9%) 	2 (6.1%) 	0 	6.2 (-5.6, 18.1) 	5.9 (-5.3, 17.1) 	
EXCORIATION 	1 (6.2%) 	1 (5.9%) 	2 (6.1%) 	0 	6.2 (-5.6, 18.1) 	5.9 (-5.3, 17.1) 	
 	 	 	 	 	 	 	
Reproductive system and breast disorders 	2 (12.5%) 	0 	2 (6.1%) 	0 	12.5 (-3.7, 28.7) 	0.0 (0.0, 0.0) 	
BENIGN PROSTATIC HYPERPLASIA 	1 (6.2%) 	0 	1 (3.0%) 	0 	6.2 (-5.6, 18.1) 	0.0 (0.0, 0.0) 	
ERECTILE DYSFUNCTION 	1 (6.2%) 	0 	1 (3.0%) 	0 	6.2 (-5.6, 18.1) 	0.0 (0.0, 0.0) 	
 	 	 	 	 	 	 	
Eye disorders 	0 	1 (5.9%) 	1 (3.0%) 	1 (5.3%) 	-5.3 (-15.3, 4.8) 	0.6 (-14.4, 15.6) 	
VISION BLURRED 	0 	1 (5.9%) 	1 (3.0%) 	0 	0.0 (0.0, 0.0) 	5.9 (-5.3, 17.1) 	
CONJUNCTIVITIS 	0 	0 	0 	1 (5.3%) 	-5.3 (-15.3, 4.8) 	-5.3 (-15.3, 4.8) 	
 	 	 	 	 	 	 	
Infections and infestations 	0 	1 (5.9%) 	1 (3.0%) 	3 (15.8%) 	-15.8 (-32.2, 0.6) 	-9.9 (-29.8, 9.9) 	
NASOPHARYNGITIS 	0 	1 (5.9%) 	1 (3.0%) 	0 	0.0 (0.0, 0.0) 	5.9 (-5.3, 17.1) 	
EAR INFECTION 	0 	0 	0 	2 (10.5%) 	-10.5 (-24.3, 3.3) 	-10.5 (-24.3, 3.3) 	
INFLUENZA 	0 	0 	0 	1 (5.3%) 	-5.3 (-15.3, 4.8) 	-5.3 (-15.3, 4.8) 	
 	 	 	 	 	 	 	
Vascular disorders 	1 (6.2%) 	0 	1 (3.0%) 	0 	6.2 (-5.6, 18.1) 	0.0 (0.0, 0.0) 	
WOUND HAEMORRHAGE 	1 (6.2%) 	0 	1 (3.0%) 	0 	6.2 (-5.6, 18.1) 	0.0 (0.0, 0.0) 	
 	 	 	 	 	 	 	
Metabolism and nutrition disorders 	0 	0 	0 	1 (5.3%) 	-5.3 (-15.3, 4.8) 	-5.3 (-15.3, 4.8) 	
DECREASED APPETITE 	0 	0 	0 	1 (5.3%) 	-5.3 (-15.3, 4.8) 	-5.3 (-15.3, 4.8) 	
 	 	 	 	 	 	 	
Musculoskeletal and connective tissue disorders 	0 	0 	0 	1 (5.3%) 	-5.3 (-15.3, 4.8) 	-5.3 (-15.3, 4.8) 	
SHOULDER PAIN 	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 AE 	29 (100.0%) 	42 (82.4%) 	71 (88.8%) 	26 (78.8%) 	21.2 (7.3, 35.2) 	3.6 (-13.9, 21.0) 	
 	  	  	  	  	  	  	
Skin and subcutaneous tissue disorders 	19 (65.5%) 	21 (41.2%) 	40 (50.0%) 	10 (30.3%) 	35.2 (11.9, 58.6) 	10.9 (-9.8, 31.6) 	
PRURITUS 	10 (34.5%) 	10 (19.6%) 	20 (25.0%) 	5 (15.2%) 	19.3 (-1.9, 40.5) 	4.5 (-11.9, 20.8) 	
ERYTHEMA 	7 (24.1%) 	5 (9.8%) 	12 (15.0%) 	4 (12.1%) 	12.0 (-7.1, 31.2) 	-2.3 (-16.1, 11.5) 	
RASH 	4 (13.8%) 	7 (13.7%) 	11 (13.8%) 	1 (3.0%) 	10.8 (-3.1, 24.6) 	10.7 (-0.4, 21.8) 	
HYPERHIDROSIS 	5 (17.2%) 	3 (5.9%) 	8 (10.0%) 	1 (3.0%) 	14.2 (-0.7, 29.2) 	2.9 (-5.9, 11.6) 	
SKIN IRRITATION 	3 (10.3%) 	4 (7.8%) 	7 (8.8%) 	3 (9.1%) 	1.3 (-13.5, 16.1) 	-1.2 (-13.5, 11.0) 	
BLISTER 	1 (3.4%) 	2 (3.9%) 	3 (3.8%) 	0 	3.4 (-3.2, 10.1) 	3.9 (-1.4, 9.2) 	
RASH PRURITIC 	1 (3.4%) 	1 (2.0%) 	2 (2.5%) 	0 	3.4 (-3.2, 10.1) 	2.0 (-1.8, 5.8) 	
PRURITUS GENERALISED 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
URTICARIA 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
ALOPECIA 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
SKIN ULCER 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
 	 	 	 	 	 	 	
General disorders and administration site conditions 	13 (44.8%) 	24 (47.1%) 	37 (46.2%) 	8 (24.2%) 	20.6 (-2.7, 43.9) 	22.8 (2.8, 42.9) 	
APPLICATION SITE PRURITUS 	4 (13.8%) 	10 (19.6%) 	14 (17.5%) 	3 (9.1%) 	4.7 (-11.2, 20.6) 	10.5 (-4.1, 25.2) 	
APPLICATION SITE ERYTHEMA 	3 (10.3%) 	7 (13.7%) 	10 (12.5%) 	0 	10.3 (-0.7, 21.4) 	13.7 (4.3, 23.2) 	
APPLICATION SITE DERMATITIS 	3 (10.3%) 	6 (11.8%) 	9 (11.2%) 	2 (6.1%) 	4.3 (-9.5, 18.0) 	5.7 (-6.3, 17.7) 	
APPLICATION SITE IRRITATION 	4 (13.8%) 	4 (7.8%) 	8 (10.0%) 	1 (3.0%) 	10.8 (-3.1, 24.6) 	4.8 (-4.6, 14.2) 	
FATIGUE 	3 (10.3%) 	4 (7.8%) 	7 (8.8%) 	0 	10.3 (-0.7, 21.4) 	7.8 (0.5, 15.2) 	
APPLICATION SITE VESICLES 	2 (6.9%) 	1 (2.0%) 	3 (3.8%) 	0 	6.9 (-2.3, 16.1) 	2.0 (-1.8, 5.8) 	
MALAISE 	1 (3.4%) 	1 (2.0%) 	2 (2.5%) 	0 	3.4 (-3.2, 10.1) 	2.0 (-1.8, 5.8) 	
OEDEMA PERIPHERAL 	1 (3.4%) 	1 (2.0%) 	2 (2.5%) 	1 (3.0%) 	0.4 (-8.4, 9.3) 	-1.1 (-8.0, 5.9) 	
APPLICATION SITE BLEEDING 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
APPLICATION SITE DESQUAMATION 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
APPLICATION SITE PAIN 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
APPLICATION SITE PERSPIRATION 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
APPLICATION SITE REACTION 	1 (3.4%) 	0 	1 (1.2%) 	1 (3.0%) 	0.4 (-8.4, 9.3) 	-3.0 (-8.9, 2.8) 	
APPLICATION SITE SWELLING 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
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 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
SECRETION DISCHARGE 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
SUDDEN DEATH 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
ULCER 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
APPLICATION SITE INDURATION 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
PYREXIA 	0 	0 	0 	2 (6.1%) 	-6.1 (-14.2, 2.1) 	-6.1 (-14.2, 2.1) 	
 	 	 	 	 	 	 	
Nervous system disorders 	10 (34.5%) 	14 (27.5%) 	24 (30.0%) 	2 (6.1%) 	28.4 (9.3, 47.5) 	21.4 (6.7, 36.1) 	
DIZZINESS 	5 (17.2%) 	4 (7.8%) 	9 (11.2%) 	0 	17.2 (3.5, 31.0) 	7.8 (0.5, 15.2) 	
HEADACHE 	3 (10.3%) 	2 (3.9%) 	5 (6.2%) 	0 	10.3 (-0.7, 21.4) 	3.9 (-1.4, 9.2) 	
SYNCOPE 	1 (3.4%) 	3 (5.9%) 	4 (5.0%) 	0 	3.4 (-3.2, 10.1) 	5.9 (-0.6, 12.3) 	
SOMNOLENCE 	1 (3.4%) 	2 (3.9%) 	3 (3.8%) 	1 (3.0%) 	0.4 (-8.4, 9.3) 	0.9 (-7.0, 8.8) 	
TRANSIENT ISCHAEMIC ATTACK 	1 (3.4%) 	1 (2.0%) 	2 (2.5%) 	0 	3.4 (-3.2, 10.1) 	2.0 (-1.8, 5.8) 	
BALANCE DISORDER 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
BURNING SENSATION 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
COMPLEX PARTIAL SEIZURES 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
COORDINATION ABNORMAL 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
HEMIANOPIA HOMONYMOUS 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
HYPERSOMNIA 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
LETHARGY 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
PARAESTHESIA ORAL 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
SYNCOPE VASOVAGAL 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
PSYCHOMOTOR HYPERACTIVITY 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
 	 	 	 	 	 	 	
Cardiac disorders 	10 (34.5%) 	9 (17.6%) 	19 (23.8%) 	5 (15.2%) 	19.3 (-1.9, 40.5) 	2.5 (-13.6, 18.6) 	
SINUS BRADYCARDIA 	6 (20.7%) 	2 (3.9%) 	8 (10.0%) 	0 	20.7 (5.9, 35.4) 	3.9 (-1.4, 9.2) 	
MYOCARDIAL INFARCTION 	3 (10.3%) 	1 (2.0%) 	4 (5.0%) 	3 (9.1%) 	1.3 (-13.5, 16.1) 	-7.1 (-17.7, 3.4) 	
ATRIAL FIBRILLATION 	1 (3.4%) 	2 (3.9%) 	3 (3.8%) 	0 	3.4 (-3.2, 10.1) 	3.9 (-1.4, 9.2) 	
VENTRICULAR EXTRASYSTOLES 	1 (3.4%) 	2 (3.9%) 	3 (3.8%) 	0 	3.4 (-3.2, 10.1) 	3.9 (-1.4, 9.2) 	
ATRIAL FLUTTER 	1 (3.4%) 	1 (2.0%) 	2 (2.5%) 	0 	3.4 (-3.2, 10.1) 	2.0 (-1.8, 5.8) 	
ATRIOVENTRICULAR BLOCK FIRST DEGREE 	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 	1 (2.0%) 	1 (1.2%) 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-1.1 (-8.0, 5.9) 	
CARDIAC DISORDER 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	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) 	
SUPRAVENTRICULAR EXTRASYSTOLES 	0 	1 (2.0%) 	1 (1.2%) 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-1.1 (-8.0, 5.9) 	
SUPRAVENTRICULAR TACHYCARDIA 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
WOLFF-PARKINSON-WHITE SYNDROME 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
BUNDLE BRANCH BLOCK LEFT 	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) 	
 	 	 	 	 	 	 	
Gastrointestinal disorders 	8 (27.6%) 	8 (15.7%) 	16 (20.0%) 	4 (12.1%) 	15.5 (-4.2, 35.2) 	3.6 (-11.4, 18.5) 	
DIARRHOEA 	2 (6.9%) 	2 (3.9%) 	4 (5.0%) 	2 (6.1%) 	0.8 (-11.5, 13.1) 	-2.1 (-11.9, 7.6) 	
NAUSEA 	3 (10.3%) 	1 (2.0%) 	4 (5.0%) 	0 	10.3 (-0.7, 21.4) 	2.0 (-1.8, 5.8) 	
VOMITING 	3 (10.3%) 	1 (2.0%) 	4 (5.0%) 	0 	10.3 (-0.7, 21.4) 	2.0 (-1.8, 5.8) 	
ABDOMINAL PAIN 	0 	2 (3.9%) 	2 (2.5%) 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	0.9 (-7.0, 8.8) 	
ABDOMINAL DISCOMFORT 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
DYSPEPSIA 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
RECTAL HAEMORRHAGE 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
SALIVARY HYPERSECRETION 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
CONSTIPATION 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
HIATUS HERNIA 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
 	 	 	 	 	 	 	
Infections and infestations 	6 (20.7%) 	5 (9.8%) 	11 (13.8%) 	10 (30.3%) 	-9.6 (-31.1, 11.9) 	-20.5 (-38.2, -2.8) 	
NASOPHARYNGITIS 	3 (10.3%) 	2 (3.9%) 	5 (6.2%) 	2 (6.1%) 	4.3 (-9.5, 18.0) 	-2.1 (-11.9, 7.6) 	
INFLUENZA 	1 (3.4%) 	1 (2.0%) 	2 (2.5%) 	0 	3.4 (-3.2, 10.1) 	2.0 (-1.8, 5.8) 	
CELLULITIS 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
PNEUMONIA 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
UPPER RESPIRATORY TRACT INFECTION 	1 (3.4%) 	0 	1 (1.2%) 	5 (15.2%) 	-11.7 (-25.6, 2.2) 	-15.2 (-27.4, -2.9) 	
URINARY TRACT INFECTION 	1 (3.4%) 	0 	1 (1.2%) 	1 (3.0%) 	0.4 (-8.4, 9.3) 	-3.0 (-8.9, 2.8) 	
BRONCHITIS 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
LOCALISED INFECTION 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
 	 	 	 	 	 	 	
Psychiatric disorders 	3 (10.3%) 	5 (9.8%) 	8 (10.0%) 	5 (15.2%) 	-4.8 (-21.3, 11.7) 	-5.3 (-20.1, 9.4) 	
AGITATION 	0 	2 (3.9%) 	2 (2.5%) 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	0.9 (-7.0, 8.8) 	
CONFUSIONAL STATE 	1 (3.4%) 	1 (2.0%) 	2 (2.5%) 	1 (3.0%) 	0.4 (-8.4, 9.3) 	-1.1 (-8.0, 5.9) 	
ANXIETY 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
DELIRIUM 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
DELUSION 	1 (3.4%) 	0 	1 (1.2%) 	1 (3.0%) 	0.4 (-8.4, 9.3) 	-3.0 (-8.9, 2.8) 	
HALLUCINATION 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
INSOMNIA 	1 (3.4%) 	0 	1 (1.2%) 	1 (3.0%) 	0.4 (-8.4, 9.3) 	-3.0 (-8.9, 2.8) 	
IRRITABILITY 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
RESTLESSNESS 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
DISTURBANCE IN SEXUAL AROUSAL 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
 	 	 	 	 	 	 	
Investigations 	1 (3.4%) 	6 (11.8%) 	7 (8.8%) 	4 (12.1%) 	-8.7 (-21.6, 4.3) 	-0.4 (-14.6, 13.9) 	
BLOOD GLUCOSE INCREASED 	1 (3.4%) 	1 (2.0%) 	2 (2.5%) 	0 	3.4 (-3.2, 10.1) 	2.0 (-1.8, 5.8) 	
BODY TEMPERATURE INCREASED 	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 	1 (2.0%) 	1 (1.2%) 	2 (6.1%) 	-6.1 (-14.2, 2.1) 	-4.1 (-13.1, 4.9) 	
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 T WAVE INVERSION 	0 	1 (2.0%) 	1 (1.2%) 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-1.1 (-8.0, 5.9) 	
NASAL MUCOSA BIOPSY 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
BLOOD ALKALINE PHOSPHATASE INCREASED 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
BLOOD URINE PRESENT 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
CYSTOSCOPY 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
 	 	 	 	 	 	 	
Musculoskeletal and connective tissue disorders 	2 (6.9%) 	5 (9.8%) 	7 (8.8%) 	1 (3.0%) 	3.9 (-7.1, 14.8) 	6.8 (-3.3, 16.8) 	
BACK PAIN 	2 (6.9%) 	1 (2.0%) 	3 (3.8%) 	1 (3.0%) 	3.9 (-7.1, 14.8) 	-1.1 (-8.0, 5.9) 	
ARTHRALGIA 	1 (3.4%) 	1 (2.0%) 	2 (2.5%) 	0 	3.4 (-3.2, 10.1) 	2.0 (-1.8, 5.8) 	
MUSCLE SPASMS 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
MUSCULAR WEAKNESS 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
SHOULDER PAIN 	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 	1 (3.4%) 	5 (9.8%) 	6 (7.5%) 	3 (9.1%) 	-5.6 (-17.5, 6.2) 	0.7 (-12.0, 13.5) 	
COUGH 	1 (3.4%) 	4 (7.8%) 	5 (6.2%) 	0 	3.4 (-3.2, 10.1) 	7.8 (0.5, 15.2) 	
DYSPNOEA 	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) 	
EMPHYSEMA 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
NASAL CONGESTION 	0 	0 	0 	2 (6.1%) 	-6.1 (-14.2, 2.1) 	-6.1 (-14.2, 2.1) 	
 	 	 	 	 	 	 	
Injury, poisoning and procedural complications 	1 (3.4%) 	4 (7.8%) 	5 (6.2%) 	2 (6.1%) 	-2.6 (-13.1, 7.9) 	1.8 (-9.2, 12.8) 	
FALL 	1 (3.4%) 	2 (3.9%) 	3 (3.8%) 	1 (3.0%) 	0.4 (-8.4, 9.3) 	0.9 (-7.0, 8.8) 	
CONTUSION 	1 (3.4%) 	1 (2.0%) 	2 (2.5%) 	0 	3.4 (-3.2, 10.1) 	2.0 (-1.8, 5.8) 	
SKIN LACERATION 	0 	2 (3.9%) 	2 (2.5%) 	0 	0.0 (0.0, 0.0) 	3.9 (-1.4, 9.2) 	
FACIAL BONES FRACTURE 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
JOINT DISLOCATION 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
WOUND 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
HIP FRACTURE 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
 	 	 	 	 	 	 	
Renal and urinary disorders 	1 (3.4%) 	3 (5.9%) 	4 (5.0%) 	1 (3.0%) 	0.4 (-8.4, 9.3) 	2.9 (-5.9, 11.6) 	
DYSURIA 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
INCONTINENCE 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
MICTURITION URGENCY 	0 	1 (2.0%) 	1 (1.2%) 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-1.1 (-8.0, 5.9) 	
NEPHROLITHIASIS 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
 	 	 	 	 	 	 	
Ear and labyrinth disorders 	1 (3.4%) 	2 (3.9%) 	3 (3.8%) 	1 (3.0%) 	0.4 (-8.4, 9.3) 	0.9 (-7.0, 8.8) 	
VERTIGO 	1 (3.4%) 	1 (2.0%) 	2 (2.5%) 	0 	3.4 (-3.2, 10.1) 	2.0 (-1.8, 5.8) 	
CERUMEN IMPACTION 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
EAR PAIN 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
 	 	 	 	 	 	 	
Vascular disorders 	0 	3 (5.9%) 	3 (3.8%) 	3 (9.1%) 	-9.1 (-18.9, 0.7) 	-3.2 (-15.0, 8.5) 	
HOT FLUSH 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
HYPERTENSION 	0 	1 (2.0%) 	1 (1.2%) 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-1.1 (-8.0, 5.9) 	
HYPOTENSION 	0 	1 (2.0%) 	1 (1.2%) 	2 (6.1%) 	-6.1 (-14.2, 2.1) 	-4.1 (-13.1, 4.9) 	
ORTHOSTATIC HYPOTENSION 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
 	 	 	 	 	 	 	
Congenital, familial and genetic disorders 	1 (3.4%) 	1 (2.0%) 	2 (2.5%) 	0 	3.4 (-3.2, 10.1) 	2.0 (-1.8, 5.8) 	
VENTRICULAR SEPTAL DEFECT 	1 (3.4%) 	1 (2.0%) 	2 (2.5%) 	0 	3.4 (-3.2, 10.1) 	2.0 (-1.8, 5.8) 	
 	 	 	 	 	 	 	
Eye disorders 	1 (3.4%) 	1 (2.0%) 	2 (2.5%) 	1 (3.0%) 	0.4 (-8.4, 9.3) 	-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) 	
VISION BLURRED 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
EYE ALLERGY 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
EYE PRURITUS 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
EYE SWELLING 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
 	 	 	 	 	 	 	
Neoplasms benign, malignant and unspecified (incl cysts and polyps) 	1 (3.4%) 	1 (2.0%) 	2 (2.5%) 	0 	3.4 (-3.2, 10.1) 	2.0 (-1.8, 5.8) 	
COLON CANCER 	0 	1 (2.0%) 	1 (1.2%) 	0 	0.0 (0.0, 0.0) 	2.0 (-1.8, 5.8) 	
PROSTATE CANCER 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
 	 	 	 	 	 	 	
Endocrine disorders 	0 	1 (2.0%) 	1 (1.2%) 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-1.1 (-8.0, 5.9) 	
BLEEDING ANOVULATORY 	0 	1 (2.0%) 	1 (1.2%) 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-1.1 (-8.0, 5.9) 	
 	 	 	 	 	 	 	
Metabolism and nutrition disorders 	1 (3.4%) 	0 	1 (1.2%) 	1 (3.0%) 	0.4 (-8.4, 9.3) 	-3.0 (-8.9, 2.8) 	
INCREASED APPETITE 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
DEHYDRATION 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
 	 	 	 	 	 	 	
Reproductive system and breast disorders 	1 (3.4%) 	0 	1 (1.2%) 	1 (3.0%) 	0.4 (-8.4, 9.3) 	-3.0 (-8.9, 2.8) 	
ABNORMAL UTERINE BLEEDING 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
BENIGN PROSTATIC HYPERPLASIA 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
 	 	 	 	 	 	 	
Surgical and medical procedures 	1 (3.4%) 	0 	1 (1.2%) 	2 (6.1%) 	-2.6 (-13.1, 7.9) 	-6.1 (-14.2, 2.1) 	
ACROCHORDON EXCISION 	1 (3.4%) 	0 	1 (1.2%) 	0 	3.4 (-3.2, 10.1) 	0.0 (0.0, 0.0) 	
CATARACT OPERATION 	0 	0 	0 	1 (3.0%) 	-3.0 (-8.9, 2.8) 	-3.0 (-8.9, 2.8) 	
EYE LASER SURGERY 	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.