TSFAE02A

Subjects With Treatment-emergent Adverse Events by System Organ Class, Preferred Term, and Subgroup

Output

Code
# Program Name:              tsfae02a.R

# Prep Environment

library(envsetup)
library(tern)
library(dplyr)
library(rtables)
library(junco)

# Define script level parameters:

# - Define output ID and file location

tblid <- "TSFAE02a"
fileid <- tblid
tab_titles <- get_titles_from_file(input_path = '../../_data/', tblid)
string_map <- default_str_map


trtvar <- "TRT01A"
popfl <- "SAFFL"

subgrpvar <- "AGEGR1"
subgrpvar_f <- "Age Group: %s years"

combined_colspan_trt <- TRUE
risk_diff <- TRUE
rr_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") %>%
  select(STUDYID, USUBJID, all_of(trtvar), all_of(popfl), all_of(subgrpvar))

adae <- pharmaverseadamjnj::adae %>%
  filter(TRTEMFL == "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 together
ae <- adae %>% right_join(., adsl, 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
)

ref_path <- c("colspan_trt", " ", trtvar, ctrl_grp)

# Define layout and build table:

extra_args_rr <- list(
  denom = "n_altdf",
  denom_by = subgrpvar,
  riskdiff = FALSE,
  extrablankline = TRUE,
  .stats = c("n_altdf")
)

extra_args_rr2 <- list(
  denom = "n_altdf",
  denom_by = subgrpvar,
  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(
    subgrpvar,
    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 subgroup

  summarize_row_groups(
    subgrpvar,
    cfun = a_freq_j,
    extra_args = append(extra_args_rr, list(label_fstr = subgrpvar_f))
  ) %>%
  split_rows_by(
    "TRTEMFL",
    split_fun = keep_split_levels("Y"),
    indent_mod = -1L,
    section_div = c(" ")
  ) %>%
  summarize_row_groups(
    "TRTEMFL",
    cfun = a_freq_j,
    extra_args = append(
      extra_args_rr2,
      list(label = "Subjects with >=1 AE", 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 columns
result <- 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(subgrpvar, "*", "TRTEMFL", "*", "AEBODSYS"),
    scorefun = jj_complex_scorefun()
  )
  result <- sort_at_path(
    result,
    c(subgrpvar, "*", "TRTEMFL", "*", "AEBODSYS", "*", "AEDECOD"),
    scorefun = jj_complex_scorefun()
  )
}

# Add titles and footnotes:

result <- set_titles(result, tab_titles)

# Convert to tbl file and output table

tt_to_tlgrtf(string_map = string_map, tt = result, file = fileid, orientation = "landscape")

TSFAE02a: Subjects With Treatment-emergent 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 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: Adverse events are coded using MedDRA version 26.0.

Download RTF file