# Program Name: tsfae03a.R# Prep Environmentlibrary(envsetup)library(tern)library(dplyr)library(rtables)library(junco)# Define script level parameters:# - Define output ID and file locationtblid <-"TSFAE03a"fileid <- tblidtab_titles <-get_titles_from_file(input_path ='../../_data/', tblid)string_map <- default_str_maptrtvar <-"TRT01A"popfl <-"SAFFL"subgrpvar <-"AGEGR1"subgrptxt <-"Age Group"subgrpunit <-"years"combined_colspan_trt <-TRUErisk_diff <-TRUErr_method <-"wald"ctrl_grp <-"Placebo"if (combined_colspan_trt ==TRUE) {# Set up levels and label for the required combined columns add_combo <-add_combo_facet("Combined",label ="Combined",levels =c("Xanomeline High Dose", "Xanomeline Low Dose") )# choose if any facets need to be removed - e.g remove the combined column for placebo rm_combo_from_placebo <-cond_rm_facets(facets ="Combined",ancestor_pos =NA,value =" ",split ="colspan_trt" ) mysplit <-make_split_fun(post =list(add_combo, rm_combo_from_placebo))}# Process Data:adsl <- pharmaverseadamjnj::adsl %>%filter(!!rlang::sym(popfl) =="Y") %>%mutate(subgrpdisplay =as.factor(paste0( subgrptxt,": ",!!as.name(subgrpvar)," ", subgrpunit )) ) %>%select( STUDYID, USUBJID,all_of(trtvar),all_of(popfl),all_of(subgrpvar), subgrpdisplay )adae <- pharmaverseadamjnj::adae %>%filter(TRTEMFL =="Y"& AESER =="Y") %>%select(USUBJID, TRTEMFL, AEBODSYS, AEDECOD)adsl$colspan_trt <-factor(ifelse(adsl[[trtvar]] =="Placebo", " ", "Active Study Agent"),levels =c("Active Study Agent", " "))if (risk_diff ==TRUE) { adsl$rrisk_header <-"Risk Difference (%) (95% CI)" adsl$rrisk_label <-paste(adsl[[trtvar]], paste("vs", ctrl_grp))}# join data togetherae <-left_join(adsl, adae, by =c("USUBJID"))colspan_trt_map <-create_colspan_map( adsl,non_active_grp = ctrl_grp,non_active_grp_span_lbl =" ",active_grp_span_lbl ="Active Study Agent",colspan_var ="colspan_trt",trt_var = trtvar)# Define layout and build table:ref_path <-c("colspan_trt", " ", "TRT01A", "Placebo")extra_args_rr <-list(denom ="n_altdf",denom_by ="subgrpdisplay",riskdiff =FALSE,extrablankline =TRUE,.stats =c("n_altdf"))extra_args_rr2 <-list(denom ="n_altdf",denom_by ="subgrpdisplay",riskdiff =TRUE,ref_path = ref_path,method ="wald",.stats =c("count_unique_fraction"))lyt <-basic_table(top_level_section_div =" ",show_colcounts =TRUE,colcount_format ="N=xx") %>%split_cols_by("colspan_trt",split_fun =trim_levels_to_map(map = colspan_trt_map) )if (combined_colspan_trt ==TRUE) { lyt <- lyt %>%split_cols_by(trtvar, split_fun = mysplit)} else { lyt <- lyt %>%split_cols_by(trtvar)}if (risk_diff ==TRUE) { lyt <- lyt %>%split_cols_by("rrisk_header", nested =FALSE) %>%split_cols_by( trtvar,labels_var ="rrisk_label",split_fun =remove_split_levels("Placebo") )}lyt <- lyt %>%split_rows_by("subgrpdisplay",split_label ="",split_fun =trim_levels_in_group("STUDYID"),indent_mod =-1L,section_div =c(" "),page_by =TRUE ) %>%# Set page_by = FALSE if you do not wish to start a new page after a new subgroupsummarize_row_groups("subgrpdisplay",cfun = a_freq_j,indent_mod =0L,extra_args = extra_args_rr ) %>%split_rows_by("TRTEMFL",split_fun =keep_split_levels("Y"),indent_mod =-1L,section_div =c(" ") ) %>%summarize_row_groups("TRTEMFL",cfun = a_freq_j,indent_mod =0L,extra_args =append( extra_args_rr2,list(label ="Subjects with >=1 SAE", extrablankline =TRUE) ) ) %>%split_rows_by("AEBODSYS",split_label ="System Organ Class",split_fun =trim_levels_in_group("AEDECOD"),label_pos ="topleft",indent_mod =0L,section_div =c(" ") ) %>%summarize_row_groups("AEBODSYS",cfun = a_freq_j,extra_args = extra_args_rr2 ) %>%analyze("AEDECOD", afun = a_freq_j, extra_args = extra_args_rr2) %>%append_topleft(" Preferred Term, n (%)")result <-build_table(lyt, ae, alt_counts_df = adsl)## Remove the N=xx column headers for the risk difference columnsresult <-remove_col_count(result)# Post-Processing step to sort by descending count on chosen active treatment columns.if (length(adae$TRTEMFL) !=0) { result <-sort_at_path( result,c("subgrpdisplay", "*", "TRTEMFL", "*", "AEBODSYS"),scorefun =jj_complex_scorefun() ) result <-sort_at_path( result,c("subgrpdisplay", "*", "TRTEMFL", "*", "AEBODSYS", "*", "AEDECOD"),scorefun =jj_complex_scorefun() )}# Add titles and footnotes:result <-set_titles(result, tab_titles)# Convert to tbl file and output tablett_to_tlgrtf(string_map = string_map, tt = result, file = fileid, orientation ="landscape")
TSFAE03a:Subjects With Treatment-emergent Serious Adverse Events by System Organ Class, Preferred Term, and [Subgroup]; Safety Analysis Set (Study jjcs - core)
Active Study Agent
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 SAE
7 (87.5%)
4 (80.0%)
11 (84.6%)
3 (42.9%)
44.6 (1.4, 87.9)
37.1 (-13.6, 87.9)
General disorders and administration site conditions
6 (75.0%)
3 (60.0%)
9 (69.2%)
2 (28.6%)
46.4 (1.5, 91.4)
31.4 (-23.0, 85.9)
APPLICATION SITE PRURITUS
3 (37.5%)
3 (60.0%)
6 (46.2%)
1 (14.3%)
23.2 (-19.2, 65.6)
45.7 (-4.4, 95.9)
APPLICATION SITE ERYTHEMA
4 (50.0%)
1 (20.0%)
5 (38.5%)
0
50.0 (15.4, 84.6)
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%)
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)
ASTHENIA
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)
COUGH
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)
NASAL CONGESTION
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)
RHINORRHOEA
1 (12.5%)
0
1 (7.7%)
0
12.5 (-10.4, 35.4)
0.0 (0.0, 0.0)
Gastrointestinal disorders
3 (37.5%)
0
3 (23.1%)
1 (14.3%)
23.2 (-19.2, 65.6)
-14.3 (-40.2, 11.6)
SALIVARY HYPERSECRETION
2 (25.0%)
0
2 (15.4%)
0
25.0 (-5.0, 55.0)
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)
Skin and subcutaneous tissue disorders
2 (25.0%)
1 (20.0%)
3 (23.1%)
2 (28.6%)
-3.6 (-48.5, 41.4)
-8.6 (-57.0, 39.9)
ERYTHEMA
2 (25.0%)
1 (20.0%)
3 (23.1%)
1 (14.3%)
10.7 (-28.9, 50.4)
5.7 (-37.9, 49.3)
PRURITUS
1 (12.5%)
1 (20.0%)
2 (15.4%)
0
12.5 (-10.4, 35.4)
20.0 (-15.1, 55.1)
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)
Infections and infestations
2 (25.0%)
0
2 (15.4%)
1 (14.3%)
10.7 (-28.9, 50.4)
-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)
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)
VAGINAL MYCOSIS
0
0
0
1 (14.3%)
-14.3 (-40.2, 11.6)
-14.3 (-40.2, 11.6)
Nervous system disorders
2 (25.0%)
0
2 (15.4%)
0
25.0 (-5.0, 55.0)
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)
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
1 (12.5%)
0
1 (7.7%)
0
12.5 (-10.4, 35.4)
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)
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%)
0
12.5 (-10.4, 35.4)
0.0 (0.0, 0.0)
CALCULUS URETHRAL
1 (12.5%)
0
1 (7.7%)
0
12.5 (-10.4, 35.4)
0.0 (0.0, 0.0)
Cardiac disorders
0
0
0
1 (14.3%)
-14.3 (-40.2, 11.6)
-14.3 (-40.2, 11.6)
ATRIOVENTRICULAR BLOCK SECOND DEGREE
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 SAE
13 (81.2%)
14 (82.4%)
27 (81.8%)
11 (57.9%)
23.4 (-5.9, 52.7)
24.5 (-4.2, 53.1)
General disorders and administration site conditions
5 (31.2%)
9 (52.9%)
14 (42.4%)
5 (26.3%)
4.9 (-25.2, 35.1)
26.6 (-4.3, 57.5)
APPLICATION SITE PRURITUS
3 (18.8%)
3 (17.6%)
6 (18.2%)
0
18.8 (-0.4, 37.9)
17.6 (-0.5, 35.8)
APPLICATION SITE 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)
APPLICATION SITE IRRITATION
1 (6.2%)
2 (11.8%)
3 (9.1%)
0
6.2 (-5.6, 18.1)
11.8 (-3.6, 27.1)
APPLICATION SITE VESICLES
1 (6.2%)
1 (5.9%)
2 (6.1%)
0
6.2 (-5.6, 18.1)
5.9 (-5.3, 17.1)
APPLICATION SITE DERMATITIS
1 (6.2%)
0
1 (3.0%)
3 (15.8%)
-9.5 (-29.8, 10.7)
-15.8 (-32.2, 0.6)
APPLICATION SITE URTICARIA
0
1 (5.9%)
1 (3.0%)
0
0.0 (0.0, 0.0)
5.9 (-5.3, 17.1)
CHEST DISCOMFORT
0
1 (5.9%)
1 (3.0%)
0
0.0 (0.0, 0.0)
5.9 (-5.3, 17.1)
FATIGUE
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
8 (50.0%)
4 (23.5%)
12 (36.4%)
3 (15.8%)
34.2 (4.7, 63.7)
7.7 (-18.2, 33.7)
PRURITUS
5 (31.2%)
3 (17.6%)
8 (24.2%)
0
31.2 (8.5, 54.0)
17.6 (-0.5, 35.8)
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)
ERYTHEMA
0
2 (11.8%)
2 (6.1%)
0
0.0 (0.0, 0.0)
11.8 (-3.6, 27.1)
RASH
1 (6.2%)
1 (5.9%)
2 (6.1%)
2 (10.5%)
-4.3 (-22.5, 13.9)
-4.6 (-22.4, 13.1)
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
4 (25.0%)
1 (5.9%)
5 (15.2%)
2 (10.5%)
14.5 (-10.8, 39.8)
-4.6 (-22.4, 13.1)
DIZZINESS
1 (6.2%)
1 (5.9%)
2 (6.1%)
0
6.2 (-5.6, 18.1)
5.9 (-5.3, 17.1)
HEADACHE
1 (6.2%)
1 (5.9%)
2 (6.1%)
1 (5.3%)
1.0 (-14.6, 16.5)
0.6 (-14.4, 15.6)
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
1 (6.2%)
1 (5.9%)
2 (6.1%)
3 (15.8%)
-9.5 (-29.8, 10.7)
-9.9 (-29.8, 9.9)
BLOOD CHOLESTEROL INCREASED
1 (6.2%)
0
1 (3.0%)
0
6.2 (-5.6, 18.1)
0.0 (0.0, 0.0)
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)
ELECTROCARDIOGRAM T WAVE INVERSION
0
0
0
1 (5.3%)
-5.3 (-15.3, 4.8)
-5.3 (-15.3, 4.8)
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)
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)
ALLERGIC GRANULOMATOUS ANGIITIS
1 (6.2%)
0
1 (3.0%)
0
6.2 (-5.6, 18.1)
0.0 (0.0, 0.0)
DYSPHONIA
0
1 (5.9%)
1 (3.0%)
0
0.0 (0.0, 0.0)
5.9 (-5.3, 17.1)
POSTNASAL DRIP
0
0
0
1 (5.3%)
-5.3 (-15.3, 4.8)
-5.3 (-15.3, 4.8)
Cardiac disorders
0
1 (5.9%)
1 (3.0%)
1 (5.3%)
-5.3 (-15.3, 4.8)
0.6 (-14.4, 15.6)
SINUS BRADYCARDIA
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)
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)
Gastrointestinal disorders
1 (6.2%)
0
1 (3.0%)
2 (10.5%)
-4.3 (-22.5, 13.9)
-10.5 (-24.3, 3.3)
VOMITING
1 (6.2%)
0
1 (3.0%)
0
6.2 (-5.6, 18.1)
0.0 (0.0, 0.0)
DIARRHOEA
0
0
0
1 (5.3%)
-5.3 (-15.3, 4.8)
-5.3 (-15.3, 4.8)
GLOSSITIS
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%)
1 (5.3%)
-5.3 (-15.3, 4.8)
0.6 (-14.4, 15.6)
NASOPHARYNGITIS
0
1 (5.9%)
1 (3.0%)
0
0.0 (0.0, 0.0)
5.9 (-5.3, 17.1)
INFLUENZA
0
0
0
1 (5.3%)
-5.3 (-15.3, 4.8)
-5.3 (-15.3, 4.8)
Injury, poisoning and procedural complications
0
1 (5.9%)
1 (3.0%)
0
0.0 (0.0, 0.0)
5.9 (-5.3, 17.1)
EXCORIATION
0
1 (5.9%)
1 (3.0%)
0
0.0 (0.0, 0.0)
5.9 (-5.3, 17.1)
Psychiatric disorders
0
1 (5.9%)
1 (3.0%)
0
0.0 (0.0, 0.0)
5.9 (-5.3, 17.1)
CONFUSIONAL STATE
0
1 (5.9%)
1 (3.0%)
0
0.0 (0.0, 0.0)
5.9 (-5.3, 17.1)
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)
Age Group: ≥75 years
29
51
80
33
Subjects with ≥1 SAE
27 (93.1%)
36 (70.6%)
63 (78.8%)
23 (69.7%)
23.4 (5.2, 41.6)
0.9 (-19.2, 20.9)
Skin and subcutaneous tissue disorders
17 (58.6%)
16 (31.4%)
33 (41.2%)
8 (24.2%)
34.4 (11.2, 57.5)
7.1 (-12.3, 26.5)
PRURITUS
6 (20.7%)
6 (11.8%)
12 (15.0%)
3 (9.1%)
11.6 (-6.1, 29.3)
2.7 (-10.5, 15.9)
ERYTHEMA
7 (24.1%)
3 (5.9%)
10 (12.5%)
3 (9.1%)
15.0 (-3.4, 33.5)
-3.2 (-15.0, 8.5)
HYPERHIDROSIS
3 (10.3%)
3 (5.9%)
6 (7.5%)
1 (3.0%)
7.3 (-5.2, 19.8)
2.9 (-5.9, 11.6)
SKIN IRRITATION
2 (6.9%)
3 (5.9%)
5 (6.2%)
3 (9.1%)
-2.2 (-15.7, 11.3)
-3.2 (-15.0, 8.5)
RASH
1 (3.4%)
3 (5.9%)
4 (5.0%)
1 (3.0%)
0.4 (-8.4, 9.3)
2.9 (-5.9, 11.6)
RASH PRURITIC
1 (3.4%)
1 (2.0%)
2 (2.5%)
0
3.4 (-3.2, 10.1)
2.0 (-1.8, 5.8)
BLISTER
0
1 (2.0%)
1 (1.2%)
0
0.0 (0.0, 0.0)
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)
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
10 (34.5%)
16 (31.4%)
26 (32.5%)
4 (12.1%)
22.4 (1.8, 42.9)
19.3 (2.3, 36.2)
APPLICATION SITE ERYTHEMA
2 (6.9%)
5 (9.8%)
7 (8.8%)
0
6.9 (-2.3, 16.1)
9.8 (1.6, 18.0)
APPLICATION SITE PRURITUS
3 (10.3%)
4 (7.8%)
7 (8.8%)
2 (6.1%)
4.3 (-9.5, 18.0)
1.8 (-9.2, 12.8)
APPLICATION SITE DERMATITIS
2 (6.9%)
4 (7.8%)
6 (7.5%)
1 (3.0%)
3.9 (-7.1, 14.8)
4.8 (-4.6, 14.2)
APPLICATION SITE IRRITATION
2 (6.9%)
2 (3.9%)
4 (5.0%)
1 (3.0%)
3.9 (-7.1, 14.8)
0.9 (-7.0, 8.8)
FATIGUE
2 (6.9%)
2 (3.9%)
4 (5.0%)
0
6.9 (-2.3, 16.1)
3.9 (-1.4, 9.2)
APPLICATION SITE VESICLES
2 (6.9%)
0
2 (2.5%)
0
6.9 (-2.3, 16.1)
0.0 (0.0, 0.0)
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 REACTION
1 (3.4%)
0
1 (1.2%)
1 (3.0%)
0.4 (-8.4, 9.3)
-3.0 (-8.9, 2.8)
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)
MALAISE
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)
Nervous system disorders
5 (17.2%)
9 (17.6%)
14 (17.5%)
1 (3.0%)
14.2 (-0.7, 29.2)
14.6 (2.6, 26.6)
DIZZINESS
2 (6.9%)
2 (3.9%)
4 (5.0%)
0
6.9 (-2.3, 16.1)
3.9 (-1.4, 9.2)
HEADACHE
1 (3.4%)
2 (3.9%)
3 (3.8%)
0
3.4 (-3.2, 10.1)
3.9 (-1.4, 9.2)
SOMNOLENCE
0
2 (3.9%)
2 (2.5%)
1 (3.0%)
-3.0 (-8.9, 2.8)
0.9 (-7.0, 8.8)
BURNING SENSATION
1 (3.4%)
0
1 (1.2%)
0
3.4 (-3.2, 10.1)
0.0 (0.0, 0.0)
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)
LETHARGY
0
1 (2.0%)
1 (1.2%)
0
0.0 (0.0, 0.0)
2.0 (-1.8, 5.8)
SYNCOPE
1 (3.4%)
0
1 (1.2%)
0
3.4 (-3.2, 10.1)
0.0 (0.0, 0.0)
TRANSIENT ISCHAEMIC ATTACK
0
1 (2.0%)
1 (1.2%)
0
0.0 (0.0, 0.0)
2.0 (-1.8, 5.8)
Cardiac disorders
6 (20.7%)
6 (11.8%)
12 (15.0%)
3 (9.1%)
11.6 (-6.1, 29.3)
2.7 (-10.5, 15.9)
SINUS BRADYCARDIA
3 (10.3%)
1 (2.0%)
4 (5.0%)
0
10.3 (-0.7, 21.4)
2.0 (-1.8, 5.8)
MYOCARDIAL INFARCTION
2 (6.9%)
1 (2.0%)
3 (3.8%)
2 (6.1%)
0.8 (-11.5, 13.1)
-4.1 (-13.1, 4.9)
ATRIAL FLUTTER
1 (3.4%)
1 (2.0%)
2 (2.5%)
0
3.4 (-3.2, 10.1)
2.0 (-1.8, 5.8)
VENTRICULAR EXTRASYSTOLES
0
2 (3.9%)
2 (2.5%)
0
0.0 (0.0, 0.0)
3.9 (-1.4, 9.2)
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)
WOLFF-PARKINSON-WHITE SYNDROME
0
1 (2.0%)
1 (1.2%)
0
0.0 (0.0, 0.0)
2.0 (-1.8, 5.8)
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)
Gastrointestinal disorders
6 (20.7%)
5 (9.8%)
11 (13.8%)
1 (3.0%)
17.7 (1.8, 33.5)
6.8 (-3.3, 16.8)
DIARRHOEA
2 (6.9%)
2 (3.9%)
4 (5.0%)
0
6.9 (-2.3, 16.1)
3.9 (-1.4, 9.2)
NAUSEA
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)
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)
VOMITING
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)
Infections and infestations
3 (10.3%)
4 (7.8%)
7 (8.8%)
8 (24.2%)
-13.9 (-32.2, 4.5)
-16.4 (-32.8, -0.0)
NASOPHARYNGITIS
2 (6.9%)
2 (3.9%)
4 (5.0%)
2 (6.1%)
0.8 (-11.5, 13.1)
-2.1 (-11.9, 7.6)
CELLULITIS
0
1 (2.0%)
1 (1.2%)
0
0.0 (0.0, 0.0)
2.0 (-1.8, 5.8)
INFLUENZA
1 (3.4%)
0
1 (1.2%)
0
3.4 (-3.2, 10.1)
0.0 (0.0, 0.0)
PNEUMONIA
0
1 (2.0%)
1 (1.2%)
0
0.0 (0.0, 0.0)
2.0 (-1.8, 5.8)
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)
UPPER RESPIRATORY TRACT INFECTION
0
0
0
3 (9.1%)
-9.1 (-18.9, 0.7)
-9.1 (-18.9, 0.7)
URINARY TRACT INFECTION
0
0
0
1 (3.0%)
-3.0 (-8.9, 2.8)
-3.0 (-8.9, 2.8)
Injury, poisoning and procedural complications
1 (3.4%)
4 (7.8%)
5 (6.2%)
1 (3.0%)
0.4 (-8.4, 9.3)
4.8 (-4.6, 14.2)
FALL
1 (3.4%)
2 (3.9%)
3 (3.8%)
0
3.4 (-3.2, 10.1)
3.9 (-1.4, 9.2)
SKIN LACERATION
0
2 (3.9%)
2 (2.5%)
0
0.0 (0.0, 0.0)
3.9 (-1.4, 9.2)
CONTUSION
0
1 (2.0%)
1 (1.2%)
0
0.0 (0.0, 0.0)
2.0 (-1.8, 5.8)
FACIAL BONES FRACTURE
1 (3.4%)
0
1 (1.2%)
0
3.4 (-3.2, 10.1)
0.0 (0.0, 0.0)
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)
Investigations
1 (3.4%)
3 (5.9%)
4 (5.0%)
4 (12.1%)
-8.7 (-21.6, 4.3)
-6.2 (-19.1, 6.6)
BLOOD GLUCOSE INCREASED
1 (3.4%)
0
1 (1.2%)
0
3.4 (-3.2, 10.1)
0.0 (0.0, 0.0)
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)
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)
Musculoskeletal and connective tissue disorders
2 (6.9%)
2 (3.9%)
4 (5.0%)
0
6.9 (-2.3, 16.1)
3.9 (-1.4, 9.2)
BACK PAIN
2 (6.9%)
0
2 (2.5%)
0
6.9 (-2.3, 16.1)
0.0 (0.0, 0.0)
ARTHRALGIA
1 (3.4%)
0
1 (1.2%)
0
3.4 (-3.2, 10.1)
0.0 (0.0, 0.0)
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)
Psychiatric disorders
1 (3.4%)
2 (3.9%)
3 (3.8%)
4 (12.1%)
-8.7 (-21.6, 4.3)
-8.2 (-20.5, 4.1)
ANXIETY
0
1 (2.0%)
1 (1.2%)
0
0.0 (0.0, 0.0)
2.0 (-1.8, 5.8)
CONFUSIONAL STATE
1 (3.4%)
0
1 (1.2%)
1 (3.0%)
0.4 (-8.4, 9.3)
-3.0 (-8.9, 2.8)
INSOMNIA
1 (3.4%)
0
1 (1.2%)
1 (3.0%)
0.4 (-8.4, 9.3)
-3.0 (-8.9, 2.8)
RESTLESSNESS
0
1 (2.0%)
1 (1.2%)
0
0.0 (0.0, 0.0)
2.0 (-1.8, 5.8)
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)
Respiratory, thoracic and mediastinal disorders
1 (3.4%)
2 (3.9%)
3 (3.8%)
0
3.4 (-3.2, 10.1)
3.9 (-1.4, 9.2)
COUGH
1 (3.4%)
1 (2.0%)
2 (2.5%)
0
3.4 (-3.2, 10.1)
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)
Ear and labyrinth disorders
0
2 (3.9%)
2 (2.5%)
0
0.0 (0.0, 0.0)
3.9 (-1.4, 9.2)
CERUMEN IMPACTION
0
1 (2.0%)
1 (1.2%)
0
0.0 (0.0, 0.0)
2.0 (-1.8, 5.8)
VERTIGO
0
1 (2.0%)
1 (1.2%)
0
0.0 (0.0, 0.0)
2.0 (-1.8, 5.8)
Renal and urinary disorders
0
2 (3.9%)
2 (2.5%)
1 (3.0%)
-3.0 (-8.9, 2.8)
0.9 (-7.0, 8.8)
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
0
0
1 (3.0%)
-3.0 (-8.9, 2.8)
-3.0 (-8.9, 2.8)
Endocrine disorders
0
1 (2.0%)
1 (1.2%)
0
0.0 (0.0, 0.0)
2.0 (-1.8, 5.8)
BLEEDING ANOVULATORY
0
1 (2.0%)
1 (1.2%)
0
0.0 (0.0, 0.0)
2.0 (-1.8, 5.8)
Eye disorders
1 (3.4%)
0
1 (1.2%)
1 (3.0%)
0.4 (-8.4, 9.3)
-3.0 (-8.9, 2.8)
VISION BLURRED
1 (3.4%)
0
1 (1.2%)
0
3.4 (-3.2, 10.1)
0.0 (0.0, 0.0)
EYE PRURITUS
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)
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
0
0
0
2 (6.1%)
-6.1 (-14.2, 2.1)
-6.1 (-14.2, 2.1)
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)
Vascular disorders
0
0
0
2 (6.1%)
-6.1 (-14.2, 2.1)
-6.1 (-14.2, 2.1)
HYPOTENSION
0
0
0
1 (3.0%)
-3.0 (-8.9, 2.8)
-3.0 (-8.9, 2.8)
ORTHOSTATIC 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: Adverse events are coded using MedDRA version 26.0.