TSFAE17A

Subjects With Treatment-emergent Serious Adverse Events by Organ System, OCMQ (Narrow) / (Broad) and Preferred Term

Output

Code
# Program Name:              tsfae17a.R

# Prep Environment

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

# Define script level parameters:

# - Define output ID and file location

tblid <- "TSFAE17a"
fileid <- tblid
tab_titles <- get_titles_from_file(input_path = '../../_data/', tblid)
string_map <- default_str_map


trtvar <- "TRT01A"
popfl <- "SAFFL"
ocmqclass <- "Narrow"
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))

adae <- pharmaverseadamjnj::adaeocmq %>%
  filter(TRTEMFL == "Y" & AESER == "Y" & OCMQCLSS == ocmqclass) %>%
  select(USUBJID, TRTEMFL, OCMQSOC, OCMQNAM, 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
)

# Define layout and build table:

ref_path <- c("colspan_trt", " ", "TRT01A", "Placebo")
extra_args_rr <- list(
  method = rr_method,
  ref_path = ref_path,
  .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(
    "OCMQSOC",
    split_label = "Organ System~[super a]",
    split_fun = trim_levels_in_group("OCMQNAM"),
    label_pos = "topleft",
    section_div = c(" "),
    nested = FALSE
  ) %>%
  summarize_row_groups(
    "OCMQSOC",
    cfun = a_freq_j,
    extra_args = append(extra_args_rr, NULL)
  ) %>%
  split_rows_by(
    "OCMQNAM",
    split_label = paste0("OCMQ (", ocmqclass, ")"),
    split_fun = trim_levels_in_group("AEDECOD"),
    label_pos = "topleft",
    nested = TRUE
  ) %>%
  summarize_row_groups(
    "OCMQNAM",
    cfun = a_freq_j,
    extra_args = append(extra_args_rr, NULL)
  ) %>%
  analyze(
    "AEDECOD",
    afun = a_freq_j,
    extra_args = append(extra_args_rr, NULL)
  ) %>%
  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)

# If there is no data display "No data to display" text
if (nrow(adae) == 0) {
  result <- safe_prune_table(result)
}

# Post-Processing step to sort by descending count on chosen active treatment columns.

if (nrow(adae) != 0) {
  result <- sort_at_path(
    result,
    c("root", "OCMQSOC"),
    scorefun = jj_complex_scorefun()
  )
  result <- sort_at_path(
    result,
    c("root", "OCMQSOC", "*", "OCMQNAM"),
    scorefun = jj_complex_scorefun()
  )
  result <- sort_at_path(
    result,
    c("root", "OCMQSOC", "*", "OCMQNAM", "*", "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")

TSFAE17a: Subjects With Treatment-emergent Serious Adverse Events by System Organ Class, FDA Medical Query (Narrow) and Preferred Term; Safety Analysis Set (Study jjcs - core)

Organ Systema

Active Study Agent

Risk Difference (%) (95% CI)

OCMQ (Narrow)

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

Skin and subcutaneous tissue
 disorders

34 (64.2%)

28 (38.4%)

62 (49.2%)

11 (18.6%)

45.5 (29.2, 61.8)

19.7 (4.8, 34.7)

Pruritus

24 (45.3%)

21 (28.8%)

45 (35.7%)

6 (10.2%)

35.1 (19.7, 50.6)

18.6 (5.7, 31.5)

PRURITUS

12 (22.6%)

10 (13.7%)

22 (17.5%)

3 (5.1%)

17.6 (5.0, 30.1)

8.6 (-1.1, 18.3)

APPLICATION SITE PRURITUS

9 (17.0%)

10 (13.7%)

19 (15.1%)

3 (5.1%)

11.9 (0.3, 23.5)

8.6 (-1.1, 18.3)

RASH PRURITIC

2 (3.8%)

1 (1.4%)

3 (2.4%)

0

3.8 (-1.4, 8.9)

1.4 (-1.3, 4.0)

PRURITUS GENERALISED

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

EYE PRURITUS

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Erythema

16 (30.2%)

14 (19.2%)

30 (23.8%)

5 (8.5%)

21.7 (7.5, 36.0)

10.7 (-0.8, 22.2)

APPLICATION SITE
 ERYTHEMA

8 (15.1%)

8 (11.0%)

16 (12.7%)

1 (1.7%)

13.4 (3.2, 23.6)

9.3 (1.4, 17.2)

ERYTHEMA

9 (17.0%)

6 (8.2%)

15 (11.9%)

4 (6.8%)

10.2 (-1.8, 22.2)

1.4 (-7.6, 10.4)

Rash

10 (18.9%)

8 (11.0%)

18 (14.3%)

4 (6.8%)

12.1 (-0.2, 24.4)

4.2 (-5.4, 13.8)

RASH

2 (3.8%)

4 (5.5%)

6 (4.8%)

4 (6.8%)

-3.0 (-11.2, 5.2)

-1.3 (-9.6, 7.0)

APPLICATION SITE VESICLES

4 (7.5%)

1 (1.4%)

5 (4.0%)

0

7.5 (0.4, 14.7)

1.4 (-1.3, 4.0)

RASH PRURITIC

2 (3.8%)

1 (1.4%)

3 (2.4%)

0

3.8 (-1.4, 8.9)

1.4 (-1.3, 4.0)

URTICARIA

1 (1.9%)

1 (1.4%)

2 (1.6%)

0

1.9 (-1.8, 5.5)

1.4 (-1.3, 4.0)

BLISTER

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

RASH MACULO-PAPULAR

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Urticaria

1 (1.9%)

1 (1.4%)

2 (1.6%)

0

1.9 (-1.8, 5.5)

1.4 (-1.3, 4.0)

URTICARIA

1 (1.9%)

1 (1.4%)

2 (1.6%)

0

1.9 (-1.8, 5.5)

1.4 (-1.3, 4.0)

APPLICATION SITE URTICARIA

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

General disorders and
 administration site conditions

12 (22.6%)

16 (21.9%)

28 (22.2%)

7 (11.9%)

10.8 (-3.2, 24.7)

10.1 (-2.5, 22.6)

Local Administration Reaction

5 (9.4%)

5 (6.8%)

10 (7.9%)

4 (6.8%)

2.7 (-7.5, 12.8)

0.1 (-8.6, 8.7)

APPLICATION SITE
 DERMATITIS

3 (5.7%)

4 (5.5%)

7 (5.6%)

4 (6.8%)

-1.1 (-10.1, 7.8)

-1.3 (-9.6, 7.0)

APPLICATION SITE PAIN

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

APPLICATION SITE REACTION

1 (1.9%)

0

1 (0.8%)

1 (1.7%)

0.2 (-4.7, 5.1)

-1.7 (-5.0, 1.6)

APPLICATION SITE URTICARIA

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

Dizziness

4 (7.5%)

4 (5.5%)

8 (6.3%)

0

7.5 (0.4, 14.7)

5.5 (0.3, 10.7)

DIZZINESS

4 (7.5%)

3 (4.1%)

7 (5.6%)

0

7.5 (0.4, 14.7)

4.1 (-0.4, 8.7)

VERTIGO

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

Fatigue

4 (7.5%)

3 (4.1%)

7 (5.6%)

1 (1.7%)

5.9 (-2.0, 13.7)

2.4 (-3.2, 8.0)

FATIGUE

3 (5.7%)

2 (2.7%)

5 (4.0%)

0

5.7 (-0.6, 11.9)

2.7 (-1.0, 6.5)

MALAISE

1 (1.9%)

1 (1.4%)

2 (1.6%)

0

1.9 (-1.8, 5.5)

1.4 (-1.3, 4.0)

LETHARGY

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

LISTLESS

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

ASTHENIA

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Fall

1 (1.9%)

2 (2.7%)

3 (2.4%)

0

1.9 (-1.8, 5.5)

2.7 (-1.0, 6.5)

FALL

1 (1.9%)

2 (2.7%)

3 (2.4%)

0

1.9 (-1.8, 5.5)

2.7 (-1.0, 6.5)

Peripheral Edema

1 (1.9%)

1 (1.4%)

2 (1.6%)

2 (3.4%)

-1.5 (-7.4, 4.4)

-2.0 (-7.4, 3.3)

OEDEMA PERIPHERAL

1 (1.9%)

1 (1.4%)

2 (1.6%)

2 (3.4%)

-1.5 (-7.4, 4.4)

-2.0 (-7.4, 3.3)

Pyrexia

0

2 (2.7%)

2 (1.6%)

0

0.0 (0.0, 0.0)

2.7 (-1.0, 6.5)

BODY TEMPERATURE
 INCREASED

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

PYREXIA

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

Nervous system disorders

6 (11.3%)

8 (11.0%)

14 (11.1%)

2 (3.4%)

7.9 (-1.8, 17.6)

7.6 (-1.0, 16.1)

Headache

2 (3.8%)

3 (4.1%)

5 (4.0%)

1 (1.7%)

2.1 (-4.0, 8.2)

2.4 (-3.2, 8.0)

HEADACHE

2 (3.8%)

3 (4.1%)

5 (4.0%)

1 (1.7%)

2.1 (-4.0, 8.2)

2.4 (-3.2, 8.0)

Somnolence

0

4 (5.5%)

4 (3.2%)

1 (1.7%)

-1.7 (-5.0, 1.6)

3.8 (-2.4, 10.0)

SOMNOLENCE

0

2 (2.7%)

2 (1.6%)

1 (1.7%)

-1.7 (-5.0, 1.6)

1.0 (-3.9, 6.0)

LETHARGY

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

STUPOR

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

Confusional State

1 (1.9%)

1 (1.4%)

2 (1.6%)

1 (1.7%)

0.2 (-4.7, 5.1)

-0.3 (-4.6, 3.9)

CONFUSIONAL STATE

1 (1.9%)

1 (1.4%)

2 (1.6%)

1 (1.7%)

0.2 (-4.7, 5.1)

-0.3 (-4.6, 3.9)

Stroke and TIA

0

2 (2.7%)

2 (1.6%)

0

0.0 (0.0, 0.0)

2.7 (-1.0, 6.5)

TRANSIENT ISCHAEMIC
 ATTACK

0

2 (2.7%)

2 (1.6%)

0

0.0 (0.0, 0.0)

2.7 (-1.0, 6.5)

Paresthesia

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

BURNING SENSATION

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Seizure

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

PARTIAL SEIZURES WITH
 SECONDARY
 GENERALISATION

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Syncope

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

SYNCOPE

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Cardiac disorders

6 (11.3%)

7 (9.6%)

13 (10.3%)

5 (8.5%)

2.8 (-8.3, 13.9)

1.1 (-8.7, 10.9)

Arrhythmia

4 (7.5%)

5 (6.8%)

9 (7.1%)

3 (5.1%)

2.5 (-6.6, 11.5)

1.8 (-6.3, 9.8)

SINUS BRADYCARDIA

3 (5.7%)

2 (2.7%)

5 (4.0%)

0

5.7 (-0.6, 11.9)

2.7 (-1.0, 6.5)

ATRIAL FLUTTER

1 (1.9%)

1 (1.4%)

2 (1.6%)

0

1.9 (-1.8, 5.5)

1.4 (-1.3, 4.0)

VENTRICULAR
 EXTRASYSTOLES

0

2 (2.7%)

2 (1.6%)

0

0.0 (0.0, 0.0)

2.7 (-1.0, 6.5)

SINUS ARRHYTHMIA

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

SUPRAVENTRICULAR
 EXTRASYSTOLES

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

TACHYCARDIA

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Acute Coronary Syndrome

2 (3.8%)

1 (1.4%)

3 (2.4%)

2 (3.4%)

0.4 (-6.5, 7.3)

-2.0 (-7.4, 3.3)

MYOCARDIAL INFARCTION

2 (3.8%)

1 (1.4%)

3 (2.4%)

2 (3.4%)

0.4 (-6.5, 7.3)

-2.0 (-7.4, 3.3)

Myocardial Infarction

2 (3.8%)

1 (1.4%)

3 (2.4%)

2 (3.4%)

0.4 (-6.5, 7.3)

-2.0 (-7.4, 3.3)

MYOCARDIAL INFARCTION

2 (3.8%)

1 (1.4%)

3 (2.4%)

2 (3.4%)

0.4 (-6.5, 7.3)

-2.0 (-7.4, 3.3)

Myocardial Ischemia

2 (3.8%)

1 (1.4%)

3 (2.4%)

2 (3.4%)

0.4 (-6.5, 7.3)

-2.0 (-7.4, 3.3)

MYOCARDIAL INFARCTION

2 (3.8%)

1 (1.4%)

3 (2.4%)

2 (3.4%)

0.4 (-6.5, 7.3)

-2.0 (-7.4, 3.3)

Cardiac Conduction
 Disturbance

0

2 (2.7%)

2 (1.6%)

2 (3.4%)

-3.4 (-8.0, 1.2)

-0.7 (-6.6, 5.3)

BUNDLE BRANCH BLOCK
 RIGHT

0

1 (1.4%)

1 (0.8%)

1 (1.7%)

-1.7 (-5.0, 1.6)

-0.3 (-4.6, 3.9)

WOLFF-PARKINSON-WHITE
 SYNDROME

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

ATRIOVENTRICULAR BLOCK
 SECOND DEGREE

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Tachycardia

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

TACHYCARDIA

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Gastrointestinal disorders

8 (15.1%)

4 (5.5%)

12 (9.5%)

3 (5.1%)

10.0 (-1.1, 21.2)

0.4 (-7.3, 8.1)

Diarrhea

2 (3.8%)

2 (2.7%)

4 (3.2%)

1 (1.7%)

2.1 (-4.0, 8.2)

1.0 (-3.9, 6.0)

DIARRHOEA

2 (3.8%)

2 (2.7%)

4 (3.2%)

1 (1.7%)

2.1 (-4.0, 8.2)

1.0 (-3.9, 6.0)

Abdominal Pain

2 (3.8%)

1 (1.4%)

3 (2.4%)

1 (1.7%)

2.1 (-4.0, 8.2)

-0.3 (-4.6, 3.9)

ABDOMINAL DISCOMFORT

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

ABDOMINAL PAIN

0

1 (1.4%)

1 (0.8%)

1 (1.7%)

-1.7 (-5.0, 1.6)

-0.3 (-4.6, 3.9)

STOMACH DISCOMFORT

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Vomiting

3 (5.7%)

0

3 (2.4%)

0

5.7 (-0.6, 11.9)

0.0 (0.0, 0.0)

VOMITING

3 (5.7%)

0

3 (2.4%)

0

5.7 (-0.6, 11.9)

0.0 (0.0, 0.0)

Nausea

2 (3.8%)

0

2 (1.6%)

0

3.8 (-1.4, 8.9)

0.0 (0.0, 0.0)

NAUSEA

2 (3.8%)

0

2 (1.6%)

0

3.8 (-1.4, 8.9)

0.0 (0.0, 0.0)

Dyspepsia

0

1 (1.4%)

1 (0.8%)

1 (1.7%)

-1.7 (-5.0, 1.6)

-0.3 (-4.6, 3.9)

DYSPEPSIA

0

1 (1.4%)

1 (0.8%)

1 (1.7%)

-1.7 (-5.0, 1.6)

-0.3 (-4.6, 3.9)

Constipation

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

CONSTIPATION

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Infections and infestations

5 (9.4%)

5 (6.8%)

10 (7.9%)

7 (11.9%)

-2.4 (-13.8, 9.0)

-5.0 (-15.1, 5.1)

Nasopharyngitis

4 (7.5%)

3 (4.1%)

7 (5.6%)

5 (8.5%)

-0.9 (-11.0, 9.1)

-4.4 (-12.8, 4.1)

NASOPHARYNGITIS

2 (3.8%)

3 (4.1%)

5 (4.0%)

2 (3.4%)

0.4 (-6.5, 7.3)

0.7 (-5.8, 7.2)

RHINITIS

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

UPPER RESPIRATORY TRACT
 INFECTION

1 (1.9%)

0

1 (0.8%)

3 (5.1%)

-3.2 (-9.9, 3.5)

-5.1 (-10.7, 0.5)

Bacterial Infection

1 (1.9%)

1 (1.4%)

2 (1.6%)

1 (1.7%)

0.2 (-4.7, 5.1)

-0.3 (-4.6, 3.9)

CELLULITIS

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

HORDEOLUM

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

URINARY TRACT INFECTION

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Pneumonia

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

PNEUMONIA

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

Viral Infection

1 (1.9%)

0

1 (0.8%)

1 (1.7%)

0.2 (-4.7, 5.1)

-1.7 (-5.0, 1.6)

INFLUENZA

1 (1.9%)

0

1 (0.8%)

1 (1.7%)

0.2 (-4.7, 5.1)

-1.7 (-5.0, 1.6)

Vascular disorders

3 (5.7%)

6 (8.2%)

9 (7.1%)

3 (5.1%)

0.6 (-7.8, 8.9)

3.1 (-5.3, 11.6)

Thrombosis

2 (3.8%)

3 (4.1%)

5 (4.0%)

2 (3.4%)

0.4 (-6.5, 7.3)

0.7 (-5.8, 7.2)

MYOCARDIAL INFARCTION

2 (3.8%)

1 (1.4%)

3 (2.4%)

2 (3.4%)

0.4 (-6.5, 7.3)

-2.0 (-7.4, 3.3)

TRANSIENT ISCHAEMIC
 ATTACK

0

2 (2.7%)

2 (1.6%)

0

0.0 (0.0, 0.0)

2.7 (-1.0, 6.5)

Thrombosis Arterial

2 (3.8%)

3 (4.1%)

5 (4.0%)

2 (3.4%)

0.4 (-6.5, 7.3)

0.7 (-5.8, 7.2)

MYOCARDIAL INFARCTION

2 (3.8%)

1 (1.4%)

3 (2.4%)

2 (3.4%)

0.4 (-6.5, 7.3)

-2.0 (-7.4, 3.3)

TRANSIENT ISCHAEMIC
 ATTACK

0

2 (2.7%)

2 (1.6%)

0

0.0 (0.0, 0.0)

2.7 (-1.0, 6.5)

Hemorrhage

1 (1.9%)

3 (4.1%)

4 (3.2%)

1 (1.7%)

0.2 (-4.7, 5.1)

2.4 (-3.2, 8.0)

APPLICATION SITE BLEEDING

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

CONTUSION

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

EPISTAXIS

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

RECTAL HAEMORRHAGE

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

BLOOD URINE PRESENT

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Hypotension

0

0

0

2 (3.4%)

-3.4 (-8.0, 1.2)

-3.4 (-8.0, 1.2)

HYPOTENSION

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

ORTHOSTATIC
 HYPOTENSION

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Psychiatric disorders

1 (1.9%)

4 (5.5%)

5 (4.0%)

4 (6.8%)

-4.9 (-12.3, 2.5)

-1.3 (-9.6, 7.0)

Study Agent Abuse Potential

0

3 (4.1%)

3 (2.4%)

1 (1.7%)

-1.7 (-5.0, 1.6)

2.4 (-3.2, 8.0)

SOMNOLENCE

0

2 (2.7%)

2 (1.6%)

1 (1.7%)

-1.7 (-5.0, 1.6)

1.0 (-3.9, 6.0)

STUPOR

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

Anxiety

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

ANXIETY

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

Insomnia

1 (1.9%)

0

1 (0.8%)

1 (1.7%)

0.2 (-4.7, 5.1)

-1.7 (-5.0, 1.6)

INSOMNIA

1 (1.9%)

0

1 (0.8%)

1 (1.7%)

0.2 (-4.7, 5.1)

-1.7 (-5.0, 1.6)

Irritability

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

AGITATION

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Psychosis

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

DELUSION

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Musculoskeletal and connective
 tissue disorders

4 (7.5%)

0

4 (3.2%)

1 (1.7%)

5.9 (-2.0, 13.7)

-1.7 (-5.0, 1.6)

Back Pain

3 (5.7%)

0

3 (2.4%)

0

5.7 (-0.6, 11.9)

0.0 (0.0, 0.0)

BACK PAIN

2 (3.8%)

0

2 (1.6%)

0

3.8 (-1.4, 8.9)

0.0 (0.0, 0.0)

FLANK PAIN

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Arthralgia

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

ARTHRALGIA

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Fracture

1 (1.9%)

0

1 (0.8%)

1 (1.7%)

0.2 (-4.7, 5.1)

-1.7 (-5.0, 1.6)

FACIAL BONES FRACTURE

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

HIP FRACTURE

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Osteoporosis

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

HIP FRACTURE

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Respiratory, thoracic and
 mediastinal disorders

3 (5.7%)

1 (1.4%)

4 (3.2%)

0

5.7 (-0.6, 11.9)

1.4 (-1.3, 4.0)

Cough

3 (5.7%)

1 (1.4%)

4 (3.2%)

0

5.7 (-0.6, 11.9)

1.4 (-1.3, 4.0)

COUGH

2 (3.8%)

1 (1.4%)

3 (2.4%)

0

3.8 (-1.4, 8.9)

1.4 (-1.3, 4.0)

PRODUCTIVE COUGH

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Reproductive system and
 breast disorders

3 (5.7%)

0

3 (2.4%)

1 (1.7%)

4.0 (-3.1, 11.0)

-1.7 (-5.0, 1.6)

Sexual Dysfunction

2 (3.8%)

0

2 (1.6%)

1 (1.7%)

2.1 (-4.0, 8.2)

-1.7 (-5.0, 1.6)

ERECTILE DYSFUNCTION

1 (1.9%)

0

1 (0.8%)

1 (1.7%)

0.2 (-4.7, 5.1)

-1.7 (-5.0, 1.6)

LIBIDO DECREASED

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Abnormal Uterine Bleeding

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

ABNORMAL UTERINE
 BLEEDING

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Erectile Dysfunction

1 (1.9%)

0

1 (0.8%)

1 (1.7%)

0.2 (-4.7, 5.1)

-1.7 (-5.0, 1.6)

ERECTILE DYSFUNCTION

1 (1.9%)

0

1 (0.8%)

1 (1.7%)

0.2 (-4.7, 5.1)

-1.7 (-5.0, 1.6)

Excessive Menstrual Bleeding

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

ABNORMAL UTERINE
 BLEEDING

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Ear and labyrinth disorders

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

Vertigo

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

VERTIGO

0

1 (1.4%)

1 (0.8%)

0

0.0 (0.0, 0.0)

1.4 (-1.3, 4.0)

Endocrine disorders

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Hyperglycemia

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

BLOOD GLUCOSE INCREASED

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Metabolism and nutrition
 disorders

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Lipid Disorder

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

BLOOD CHOLESTEROL
 INCREASED

1 (1.9%)

0

1 (0.8%)

0

1.9 (-1.8, 5.5)

0.0 (0.0, 0.0)

Immune system disorders

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Hypersensitivity

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

DRUG ERUPTION

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Renal and urinary disorders

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Renal & Urinary Tract
 Infection

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

URINARY TRACT INFECTION

0

0

0

1 (1.7%)

-1.7 (-5.0, 1.6)

-1.7 (-5.0, 1.6)

Key: FMQ=FDA Medical Query

a Each FMQ is aligned to a single system organ class based on clinical judgment, as defined by FDA. However, some FMQs may contain preferred terms from more than one system organ class. Preferred terms that are not included in any FMQ are not summarized.

Note: Adverse events are coded using MedDRA version 26.0.

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