Adverse Events by Grade / Intensity

Summary of Treatment-Emergent Adverse Events by SOC, PT, and Severity Grade

Setup

See Prerequisites for installation instructions.

library(arframe)
library(pharmaverseadam)
library(dplyr, warn.conflicts = FALSE)
library(tidyr)
library(cards)

adsl_saf <- pharmaverseadam::adsl |>
  blank_to_na() |>
  filter(SAFFL == "Y", TRT01A != "Screen Failure")

adae_teae <- pharmaverseadam::adae |>
  blank_to_na() |>
  filter(TRTEMFL == "Y", TRT01A != "Screen Failure") |>
  mutate(AESEV = factor(AESEV, levels = c("MILD", "MODERATE", "SEVERE")))

arm_levels <- c("Placebo", "Xanomeline Low Dose", "Xanomeline High Dose")
sev_levels <- levels(adae_teae$AESEV)

arm_n <- adsl_saf |>
  filter(TRT01A %in% arm_levels) |>
  count(TRT01A) |>
  pull(n, name = TRT01A)
arm_n <- arm_n[arm_levels]

N_total <- nrow(adsl_saf)

Data Preparation

n_pct <- function(n, denom) sprintf("%d (%.1f)", n, n / denom * 100)

# ── Column names: Placebo_MILD, Placebo_MODERATE, ... ──
col_names <- unlist(lapply(arm_levels, function(a) {
  paste(gsub(" ", "_", a), sev_levels, sep = "_")
}))

# ── Helper: pivot arm×sev to wide, preserving any non-TRT01A/AESEV/value cols ──
pivot_arm_sev <- function(df, value_col = "value") {
  id_cols <- setdiff(names(df), c("TRT01A", "AESEV", value_col))
  df |>
    mutate(col = paste(gsub(" ", "_", TRT01A), AESEV, sep = "_")) |>
    select(all_of(id_cols), col, all_of(value_col)) |>
    pivot_wider(names_from = col, values_from = all_of(value_col))
}

# ── SOC × severity ──
soc_sev_arm <- adae_teae |>
  filter(TRT01A %in% arm_levels) |>
  distinct(USUBJID, TRT01A, AEBODSYS, AESEV) |>
  count(TRT01A, AEBODSYS, AESEV, .drop = FALSE) |>
  filter(!is.na(AEBODSYS)) |>
  mutate(value = mapply(n_pct, n, arm_n[TRT01A])) |>
  select(TRT01A, AEBODSYS, AESEV, value) |>
  pivot_arm_sev()

soc_wide <- adae_teae |>
  filter(TRT01A %in% arm_levels) |>
  distinct(USUBJID, AEBODSYS) |>
  count(AEBODSYS, name = "soc_n") |>
  left_join(soc_sev_arm, by = "AEBODSYS") |>
  mutate(
    soc      = AEBODSYS,
    pt       = AEBODSYS,
    row_type = "soc",
    .before  = 1
  ) |>
  select(-AEBODSYS, -soc_n)

# ── PT × severity ──
pt_sev_arm <- adae_teae |>
  filter(TRT01A %in% arm_levels) |>
  distinct(USUBJID, TRT01A, AEBODSYS, AEDECOD, AESEV) |>
  count(TRT01A, AEBODSYS, AEDECOD, AESEV, .drop = FALSE) |>
  filter(!is.na(AEBODSYS), !is.na(AEDECOD)) |>
  mutate(value = mapply(n_pct, n, arm_n[TRT01A])) |>
  select(TRT01A, AEBODSYS, AEDECOD, AESEV, value) |>
  pivot_arm_sev()

pt_wide <- adae_teae |>
  filter(TRT01A %in% arm_levels) |>
  distinct(USUBJID, AEBODSYS, AEDECOD) |>
  count(AEBODSYS, AEDECOD, name = "pt_n") |>
  left_join(pt_sev_arm, by = c("AEBODSYS", "AEDECOD")) |>
  mutate(
    soc      = AEBODSYS,
    pt       = AEDECOD,
    row_type = "pt",
    .before  = 1
  ) |>
  select(-AEBODSYS, -AEDECOD, -pt_n)

# ── Sort order ──
soc_order <- adae_teae |>
  distinct(USUBJID, AEBODSYS) |>
  count(AEBODSYS, name = "n") |>
  arrange(desc(n)) |>
  pull(AEBODSYS)

pt_order <- adae_teae |>
  distinct(USUBJID, AEBODSYS, AEDECOD) |>
  count(AEBODSYS, AEDECOD, name = "n") |>
  arrange(match(AEBODSYS, soc_order), desc(n)) |>
  select(soc = AEBODSYS, pt = AEDECOD)

pt_wide <- pt_order |>
  left_join(pt_wide, by = c("soc", "pt"))

# ── Interleave SOC + PT rows ──
ae_grade_wide <- bind_rows(
  lapply(soc_order, function(s) {
    bind_rows(
      filter(soc_wide, soc == s),
      filter(pt_wide, soc == s)
    )
  })
) |>
  mutate(across(all_of(col_names), ~ replace_na(.x, "0 (0.0)")))

n_vec <- arm_n

ae_grade_ard <- ard_stack_hierarchical(
  data        = adae_teae |> filter(AESEV %in% sev_levels),
  variables   = c(AEBODSYS, AEDECOD),
  by          = c(TRT01A, AESEV),
  denominator = adsl_saf,
  id          = USUBJID,
  overall     = FALSE
) |>
  sort_ard_hierarchical(sort = "descending")

# Note: cards output has a different layout (AESEV as page_by)
# than the dplyr path (arm × grade column spans matching DPP shell)
ae_grade_cards <- fr_wide_ard(
  ae_grade_ard,
  statistic = "{n} ({p}%)",
  decimals  = c(p = 1),
  label     = c(
    AEBODSYS = "System Organ Class",
    AEDECOD  = "Preferred Term"
  )
)

arframe Pipeline

The rendered table below uses the dplyr data prep (ae_grade_wide, arm x severity columns with spans). The cards tab produces ae_grade_cards with a different layout — see the cards tab for details.

# Build fr_col() list for arm × severity columns
sev_cols <- unlist(lapply(arm_levels, function(a) {
  setNames(
    lapply(sev_levels, function(s) {
      fr_col(tools::toTitleCase(tolower(s)), align = "decimal")
    }),
    paste(gsub(" ", "_", a), sev_levels, sep = "_")
  )
}), recursive = FALSE)

ae_grade_wide |>
  fr_table() |>
  fr_titles(
    "Table 14.3.4",
    "Summary of Treatment-Emergent Adverse Events by SOC, Preferred Term, and Severity Grade",
    "Safety Population"
  ) |>
  fr_cols(
    soc      = fr_col(visible = FALSE),
    pt       = fr_col("System Organ Class\n  Preferred Term", width = 3.0),
    row_type = fr_col(visible = FALSE),
    !!!sev_cols,
    .n = n_vec
  ) |>
  fr_spans(
    !!!setNames(
      lapply(arm_levels, function(a) {
        paste(gsub(" ", "_", a), sev_levels, sep = "_")
      }),
      arm_levels
    )
  ) |>
  fr_header(bold = TRUE, align = "center") |>
  fr_rows(
    group_by  = "soc",
    indent_by = "pt"
  ) |>
  fr_styles(
    fr_row_style(rows = fr_rows_matches("row_type", value = "soc"), bold = TRUE)
  ) |>
  fr_footnotes(
    "TEAE = Treatment-Emergent Adverse Event. Subjects counted once per SOC×grade and once per PT×grade.",
    "Severity grade: MILD, MODERATE, SEVERE as recorded in AESEV.",
    "Percentages based on N per treatment arm (Safety Population).",
    "SOC rows sorted by descending subject frequency; PT rows sorted within SOC by descending frequency."
  )

Rendered Table

Table 14.3.4

Summary of Treatment-Emergent Adverse Events by SOC, Preferred Term, and Severity Grade

Safety Population

	Placebo (N=86)			Xanomeline High Dose (N=72)			Xanomeline Low Dose (N=96)
System Organ Class Preferred Term	Mild	Moderate	Severe	Mild	Moderate	Severe	Mild	Moderate	Severe
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS	20 (23.3)	5 (5.8)	0	31 (43.1)	19 (26.4)	0	35 (36.5)	27 (28.1)	7 (7.3)
APPLICATION SITE PRURITUS	6 ( 7.0)	1 (1.2)	0	17 (23.6)	11 (15.3)	0	19 (19.8)	10 (10.4)	1 (1.0)
APPLICATION SITE ERYTHEMA	3 ( 3.5)	0	0	12 (16.7)	5 ( 6.9)	0	9 ( 9.4)	8 ( 8.3)	2 (2.1)
APPLICATION SITE DERMATITIS	5 ( 5.8)	0	0	6 ( 8.3)	5 ( 6.9)	0	7 ( 7.3)	4 ( 4.2)	1 (1.0)
APPLICATION SITE IRRITATION	2 ( 2.3)	2 (2.3)	0	8 (11.1)	6 ( 8.3)	0	5 ( 5.2)	6 ( 6.2)	3 (3.1)
APPLICATION SITE VESICLES	1 ( 1.2)	0	0	2 ( 2.8)	3 ( 4.2)	0	3 ( 3.1)	2 ( 2.1)	0
FATIGUE	1 ( 1.2)	0	0	5 ( 6.9)	0	0	3 ( 3.1)	2 ( 2.1)	0
OEDEMA PERIPHERAL	2 ( 2.3)	0	0	1 ( 1.4)	1 ( 1.4)	0	0	1 ( 1.0)	0
APPLICATION SITE SWELLING	0	0	0	1 ( 1.4)	1 ( 1.4)	0	1 ( 1.0)	0	0
APPLICATION SITE URTICARIA	0	0	0	0	1 ( 1.4)	0	2 ( 2.1)	0	0
CHILLS	0	1 (1.2)	0	1 ( 1.4)	0	0	1 ( 1.0)	0	0
MALAISE	0	0	0	2 ( 2.8)	1 ( 1.4)	0	1 ( 1.0)	0	0
PYREXIA	2 ( 2.3)	0	0	0	0	0	1 ( 1.0)	0	0
APPLICATION SITE PAIN	0	0	0	1 ( 1.4)	1 ( 1.4)	0	0	0	0
APPLICATION SITE PERSPIRATION	0	0	0	1 ( 1.4)	1 ( 1.4)	0	0	0	0
APPLICATION SITE REACTION	1 ( 1.2)	1 (1.2)	0	0	1 ( 1.4)	0	0	0	0
ASTHENIA	1 ( 1.2)	1 (1.2)	0	0	0	0	0	1 ( 1.0)	0
CHEST DISCOMFORT	0	0	0	1 ( 1.4)	0	0	1 ( 1.0)	0	0
CHEST PAIN	0	0	0	2 ( 2.8)	0	0	0	0	0
OEDEMA	0	0	0	0	0	0	2 ( 2.1)	0	0
PAIN	0	0	0	1 ( 1.4)	0	0	0	1 ( 1.0)	0
APPLICATION SITE BLEEDING	0	0	0	0	0	0	0	1 ( 1.0)	0
APPLICATION SITE DESQUAMATION	0	0	0	0	0	0	1 ( 1.0)	0	0
APPLICATION SITE DISCHARGE	0	0	0	0	1 ( 1.4)	0	0	0	0
APPLICATION SITE DISCOLOURATION	0	0	0	0	0	0	0	1 ( 1.0)	0
APPLICATION SITE INDURATION	1 ( 1.2)	0	0	0	0	0	0	0	0
APPLICATION SITE WARMTH	0	0	0	0	0	0	0	1 ( 1.0)	1 (1.0)
FEELING ABNORMAL	0	0	0	1 ( 1.4)	0	0	0	0	0
FEELING COLD	0	0	0	1 ( 1.4)	0	0	0	0	0
INFLAMMATION	0	0	0	0	0	0	0	1 ( 1.0)	0
SECRETION DISCHARGE	0	0	0	0	0	0	1 ( 1.0)	0	0
SUDDEN DEATH	0	0	0	0	0	0	0	0	1 (1.0)
SWELLING	0	0	0	0	0	0	0	1 ( 1.0)	0
ULCER	0	0	0	0	0	0	0	1 ( 1.0)	0
SKIN AND SUBCUTANEOUS TISSUE DISORDERS	18 (20.9)	8 (9.3)	0	35 (48.6)	15 (20.8)	1 (1.4)	19 (19.8)	26 (27.1)	4 (4.2)
PRURITUS	8 ( 9.3)	1 (1.2)	0	19 (26.4)	9 (12.5)	0	11 (11.5)	12 (12.5)	1 (1.0)
ERYTHEMA	6 ( 7.0)	4 (4.7)	0	12 (16.7)	4 ( 5.6)	0	7 ( 7.3)	8 ( 8.3)	0
RASH	4 ( 4.7)	3 (3.5)	0	6 ( 8.3)	2 ( 2.8)	1 (1.4)	11 (11.5)	3 ( 3.1)	1 (1.0)
HYPERHIDROSIS	2 ( 2.3)	0	0	8 (11.1)	0	0	1 ( 1.0)	3 ( 3.1)	0
SKIN IRRITATION	2 ( 2.3)	1 (1.2)	0	5 ( 6.9)	2 ( 2.8)	0	2 ( 2.1)	4 ( 4.2)	1 (1.0)
BLISTER	0	0	0	1 ( 1.4)	0	0	1 ( 1.0)	4 ( 4.2)	1 (1.0)
RASH PRURITIC	0	0	0	1 ( 1.4)	1 ( 1.4)	0	0	1 ( 1.0)	0
PRURITUS GENERALISED	0	0	0	1 ( 1.4)	0	0	0	1 ( 1.0)	0
URTICARIA	0	0	0	1 ( 1.4)	0	0	1 ( 1.0)	1 ( 1.0)	0
ACTINIC KERATOSIS	0	0	0	1 ( 1.4)	0	0	0	0	0
ALOPECIA	1 ( 1.2)	0	0	0	0	0	0	0	0
COLD SWEAT	0	1 (1.2)	0	0	0	0	0	0	0
DERMATITIS CONTACT	0	0	0	0	0	0	0	1 ( 1.0)	0
DRUG ERUPTION	1 ( 1.2)	0	0	0	0	0	0	0	0
RASH ERYTHEMATOUS	0	0	0	0	0	0	0	1 ( 1.0)	0
RASH MACULO-PAPULAR	0	0	0	1 ( 1.4)	0	0	0	0	0
SKIN EXFOLIATION	0	0	0	0	0	0	0	1 ( 1.0)	0
SKIN ODOUR ABNORMAL	0	0	0	1 ( 1.4)	0	0	0	0	0
SKIN ULCER	0	1 (1.2)	0	0	0	0	0	0	0
NERVOUS SYSTEM DISORDERS	6 ( 7.0)	2 (2.3)	0	18 (25.0)	8 (11.1)	4 (5.6)	15 (15.6)	9 ( 9.4)	3 (3.1)
DIZZINESS	2 ( 2.3)	0	0	7 ( 9.7)	3 ( 4.2)	1 (1.4)	7 ( 7.3)	3 ( 3.1)	0
HEADACHE	3 ( 3.5)	0	0	5 ( 6.9)	1 ( 1.4)	0	2 ( 2.1)	0	1 (1.0)
SYNCOPE	0	0	0	0	2 ( 2.8)	1 (1.4)	1 ( 1.0)	2 ( 2.1)	2 (2.1)
SOMNOLENCE	0	2 (2.3)	0	1 ( 1.4)	0	0	2 ( 2.1)	2 ( 2.1)	0
TRANSIENT ISCHAEMIC ATTACK	0	0	0	0	0	1 (1.4)	1 ( 1.0)	0	1 (1.0)
BURNING SENSATION	0	0	0	1 ( 1.4)	1 ( 1.4)	0	0	0	0
LETHARGY	0	0	0	0	1 ( 1.4)	0	0	1 ( 1.0)	0
AMNESIA	0	0	0	1 ( 1.4)	0	0	0	0	0
BALANCE DISORDER	0	0	0	0	0	0	1 ( 1.0)	1 ( 1.0)	0
COGNITIVE DISORDER	0	0	0	1 ( 1.4)	0	0	0	0	0
COMPLEX PARTIAL SEIZURES	0	0	0	0	0	0	0	1 ( 1.0)	0
COORDINATION ABNORMAL	0	0	0	0	0	0	1 ( 1.0)	0	0
HEMIANOPIA HOMONYMOUS	0	0	0	0	0	0	1 ( 1.0)	0	0
HYPERSOMNIA	0	0	0	1 ( 1.4)	0	0	0	0	0
PARAESTHESIA	0	0	0	1 ( 1.4)	0	0	0	0	0
PARAESTHESIA ORAL	0	0	0	0	0	0	1 ( 1.0)	0	0
PARKINSON'S DISEASE	1 ( 1.2)	0	0	0	0	0	0	0	0
PAROSMIA	0	0	0	1 ( 1.4)	0	0	0	0	0
PARTIAL SEIZURES WITH SECONDARY GENERALISATION	0	0	0	0	0	1 (1.4)	0	0	0
PSYCHOMOTOR HYPERACTIVITY	1 ( 1.2)	0	0	0	0	0	0	0	0
STUPOR	0	0	0	0	0	0	0	0	1 (1.0)
SYNCOPE VASOVAGAL	0	0	0	0	1 ( 1.4)	0	0	0	0
GASTROINTESTINAL DISORDERS	15 (17.4)	2 (2.3)	0	16 (22.2)	4 ( 5.6)	2 (2.8)	10 (10.4)	5 ( 5.2)	0
DIARRHOEA	9 (10.5)	0	0	2 ( 2.8)	1 ( 1.4)	0	4 ( 4.2)	1 ( 1.0)	0
VOMITING	2 ( 2.3)	1 (1.2)	0	5 ( 6.9)	1 ( 1.4)	0	2 ( 2.1)	2 ( 2.1)	0
NAUSEA	2 ( 2.3)	1 (1.2)	0	5 ( 6.9)	1 ( 1.4)	1 (1.4)	2 ( 2.1)	1 ( 1.0)	0
ABDOMINAL PAIN	1 ( 1.2)	0	0	1 ( 1.4)	1 ( 1.4)	0	2 ( 2.1)	1 ( 1.0)	0
SALIVARY HYPERSECRETION	0	0	0	4 ( 5.6)	0	0	0	0	0
DYSPEPSIA	1 ( 1.2)	0	0	0	0	0	0	1 ( 1.0)	0
ABDOMINAL DISCOMFORT	0	0	0	1 ( 1.4)	0	0	0	0	0
CONSTIPATION	1 ( 1.2)	0	0	0	0	0	0	0	0
DYSPHAGIA	0	0	0	0	0	0	0	1 ( 1.0)	0
FLATULENCE	1 ( 1.2)	0	0	0	0	0	0	0	0
GASTROINTESTINAL HAEMORRHAGE	0	0	0	0	0	1 (1.4)	0	0	0
GASTROOESOPHAGEAL REFLUX DISEASE	1 ( 1.2)	0	0	0	0	0	0	0	0
GLOSSITIS	1 ( 1.2)	0	0	0	0	0	0	0	0
HIATUS HERNIA	0	1 (1.2)	0	0	0	0	0	0	0
RECTAL HAEMORRHAGE	0	0	0	0	0	0	1 ( 1.0)	0	0
STOMACH DISCOMFORT	0	0	0	1 ( 1.4)	0	0	0	0	0
CARDIAC DISORDERS	10 (11.6)	3 (3.5)	2 (2.3)	8 (11.1)	5 ( 6.9)	1 (1.4)	12 (12.5)	5 ( 5.2)	0
SINUS BRADYCARDIA	1 ( 1.2)	1 (1.2)	0	4 ( 5.6)	4 ( 5.6)	0	6 ( 6.2)	1 ( 1.0)	0
MYOCARDIAL INFARCTION	1 ( 1.2)	1 (1.2)	2 (2.3)	3 ( 4.2)	1 ( 1.4)	0	2 ( 2.1)	0	0
ATRIAL FIBRILLATION	0	1 (1.2)	0	1 ( 1.4)	0	1 (1.4)	1 ( 1.0)	1 ( 1.0)	0
SUPRAVENTRICULAR EXTRASYSTOLES	1 ( 1.2)	0	0	1 ( 1.4)	0	0	1 ( 1.0)	0	0
VENTRICULAR EXTRASYSTOLES	0	0	0	1 ( 1.4)	0	0	1 ( 1.0)	1 ( 1.0)	0
ATRIAL FLUTTER	0	0	0	1 ( 1.4)	0	0	0	1 ( 1.0)	0
ATRIOVENTRICULAR BLOCK FIRST DEGREE	1 ( 1.2)	0	0	0	0	0	1 ( 1.0)	0	0
BUNDLE BRANCH BLOCK RIGHT	1 ( 1.2)	0	0	0	0	0	0	1 ( 1.0)	0
PALPITATIONS	0	0	0	0	0	0	0	2 ( 2.1)	0
ATRIAL HYPERTROPHY	1 ( 1.2)	0	0	0	0	0	0	0	0
ATRIOVENTRICULAR BLOCK SECOND DEGREE	1 ( 1.2)	0	0	0	0	0	0	0	0
BRADYCARDIA	1 ( 1.2)	0	0	0	0	0	0	0	0
BUNDLE BRANCH BLOCK LEFT	1 ( 1.2)	0	0	0	0	0	0	0	0
CARDIAC DISORDER	0	0	0	1 ( 1.4)	0	0	0	0	0
CARDIAC FAILURE CONGESTIVE	0	1 (1.2)	0	0	0	0	0	0	0
SINUS ARRHYTHMIA	1 ( 1.2)	0	0	0	0	0	0	0	0
SUPRAVENTRICULAR TACHYCARDIA	0	0	0	0	0	0	0	1 ( 1.0)	0
TACHYCARDIA	1 ( 1.2)	1 (1.2)	0	0	0	0	0	0	0
VENTRICULAR HYPERTROPHY	1 ( 1.2)	0	0	0	0	0	0	0	0
WOLFF-PARKINSON-WHITE SYNDROME	0	0	0	0	0	0	1 ( 1.0)	0	0
INFECTIONS AND INFESTATIONS	12 (14.0)	5 (5.8)	0	10 (13.9)	3 ( 4.2)	0	7 ( 7.3)	2 ( 2.1)	1 (1.0)
NASOPHARYNGITIS	1 ( 1.2)	1 (1.2)	0	5 ( 6.9)	1 ( 1.4)	0	4 ( 4.2)	0	1 (1.0)
UPPER RESPIRATORY TRACT INFECTION	4 ( 4.7)	2 (2.3)	0	2 ( 2.8)	1 ( 1.4)	0	1 ( 1.0)	0	0
INFLUENZA	1 ( 1.2)	0	0	1 ( 1.4)	0	0	1 ( 1.0)	0	0
URINARY TRACT INFECTION	2 ( 2.3)	0	0	1 ( 1.4)	0	0	0	0	0
CYSTITIS	1 ( 1.2)	0	0	1 ( 1.4)	0	0	0	0	0
EAR INFECTION	2 ( 2.3)	0	0	0	0	0	0	0	0
BRONCHITIS	0	1 (1.2)	0	0	0	0	0	0	0
CELLULITIS	0	0	0	0	0	0	0	1 ( 1.0)	0
CERVICITIS	1 ( 1.2)	0	0	0	0	0	0	0	0
GASTROENTERITIS VIRAL	0	1 (1.2)	0	0	0	0	0	0	0
HORDEOLUM	0	0	0	1 ( 1.4)	0	0	0	0	0
LOCALISED INFECTION	1 ( 1.2)	0	0	0	0	0	0	0	0
LOWER RESPIRATORY TRACT INFECTION	0	0	0	0	1 ( 1.4)	0	0	0	0
PNEUMONIA	0	0	0	0	0	0	0	1 ( 1.0)	0
RHINITIS	0	0	0	1 ( 1.4)	0	0	0	0	0
VAGINAL MYCOSIS	1 ( 1.2)	0	0	0	0	0	0	0	0
VIRAL INFECTION	0	0	0	0	0	0	1 ( 1.0)	0	0
PSYCHIATRIC DISORDERS	7 ( 8.1)	2 (2.3)	1 (1.2)	4 ( 5.6)	3 ( 4.2)	0	4 ( 4.2)	7 ( 7.3)	1 (1.0)
CONFUSIONAL STATE	1 ( 1.2)	1 (1.2)	0	1 ( 1.4)	0	0	0	3 ( 3.1)	0
AGITATION	2 ( 2.3)	0	0	0	0	0	0	2 ( 2.1)	1 (1.0)
INSOMNIA	2 ( 2.3)	0	0	2 ( 2.8)	0	0	0	0	0
ANXIETY	0	0	0	0	0	0	3 ( 3.1)	0	0
DELUSION	1 ( 1.2)	0	0	0	1 ( 1.4)	0	0	0	0
IRRITABILITY	0	1 (1.2)	0	0	0	0	1 ( 1.0)	0	0
COMPLETED SUICIDE	0	0	1 (1.2)	0	0	0	0	0	0
DELIRIUM	0	0	0	0	1 ( 1.4)	0	0	0	0
DEPRESSED MOOD	0	0	0	0	0	0	1 ( 1.0)	1 ( 1.0)	0
DISORIENTATION	1 ( 1.2)	0	0	0	0	0	0	0	0
HALLUCINATION	0	0	0	0	1 ( 1.4)	0	0	0	0
HALLUCINATION, VISUAL	0	0	0	0	1 ( 1.4)	0	0	0	0
LIBIDO DECREASED	0	0	0	1 ( 1.4)	0	0	0	0	0
LISTLESS	0	0	0	1 ( 1.4)	0	0	0	0	0
NIGHTMARE	0	0	0	1 ( 1.4)	0	0	0	0	0
RESTLESSNESS	0	0	0	0	0	0	0	1 ( 1.0)	0
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS	7 ( 8.1)	1 (1.2)	0	8 (11.1)	2 ( 2.8)	0	7 ( 7.3)	3 ( 3.1)	0
COUGH	1 ( 1.2)	0	0	3 ( 4.2)	2 ( 2.8)	0	3 ( 3.1)	2 ( 2.1)	0
NASAL CONGESTION	3 ( 3.5)	0	0	3 ( 4.2)	0	0	1 ( 1.0)	0	0
DYSPNOEA	0	1 (1.2)	0	1 ( 1.4)	0	0	0	1 ( 1.0)	0
EPISTAXIS	0	0	0	2 ( 2.8)	0	0	1 ( 1.0)	0	0
PHARYNGOLARYNGEAL PAIN	0	0	0	1 ( 1.4)	0	0	1 ( 1.0)	0	0
RHINORRHOEA	0	0	0	1 ( 1.4)	0	0	1 ( 1.0)	0	0
ALLERGIC GRANULOMATOUS ANGIITIS	0	0	0	1 ( 1.4)	0	0	0	0	0
DYSPHONIA	0	0	0	0	0	0	1 ( 1.0)	0	0
EMPHYSEMA	1 ( 1.2)	0	0	0	0	0	0	0	0
HAEMOPTYSIS	1 ( 1.2)	0	0	0	0	0	0	0	0
PHARYNGEAL ERYTHEMA	0	0	0	1 ( 1.4)	0	0	0	0	0
POSTNASAL DRIP	1 ( 1.2)	0	0	0	0	0	0	0	0
PRODUCTIVE COUGH	0	0	0	1 ( 1.4)	0	0	0	0	0
RALES	1 ( 1.2)	0	0	0	0	0	0	0	0
RESPIRATORY TRACT CONGESTION	0	0	0	1 ( 1.4)	0	0	0	0	0
INVESTIGATIONS	8 ( 9.3)	2 (2.3)	0	4 ( 5.6)	1 ( 1.4)	0	6 ( 6.2)	1 ( 1.0)	0
ELECTROCARDIOGRAM ST SEGMENT DEPRESSION	4 ( 4.7)	0	0	0	0	0	1 ( 1.0)	0	0
ELECTROCARDIOGRAM T WAVE INVERSION	2 ( 2.3)	0	0	1 ( 1.4)	0	0	1 ( 1.0)	0	0
BLOOD GLUCOSE INCREASED	0	0	0	1 ( 1.4)	0	0	1 ( 1.0)	0	0
ELECTROCARDIOGRAM T WAVE AMPLITUDE DECREASED	1 ( 1.2)	0	0	0	0	0	1 ( 1.0)	0	0
BIOPSY	0	0	0	1 ( 1.4)	0	0	0	0	0
BIOPSY PROSTATE	0	0	0	0	1 ( 1.4)	0	0	0	0
BLOOD ALKALINE PHOSPHATASE INCREASED	0	1 (1.2)	0	0	0	0	0	0	0
BLOOD CHOLESTEROL INCREASED	0	0	0	1 ( 1.4)	0	0	0	0	0
BLOOD CREATINE PHOSPHOKINASE INCREASED	0	1 (1.2)	0	0	0	0	0	0	0
BLOOD URINE PRESENT	1 ( 1.2)	0	0	0	0	0	0	0	0
BODY TEMPERATURE INCREASED	0	0	0	0	0	0	1 ( 1.0)	0	0
CYSTOSCOPY	1 ( 1.2)	0	0	0	0	0	0	0	0
HEART RATE INCREASED	1 ( 1.2)	0	0	0	0	0	0	0	0
HEART RATE IRREGULAR	1 ( 1.2)	0	0	0	0	0	0	0	0
NASAL MUCOSA BIOPSY	0	0	0	0	0	0	1 ( 1.0)	0	0
WEIGHT DECREASED	0	0	0	0	0	0	0	1 ( 1.0)	0
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS	4 ( 4.7)	1 (1.2)	0	4 ( 5.6)	4 ( 5.6)	0	3 ( 3.1)	4 ( 4.2)	1 (1.0)
BACK PAIN	1 ( 1.2)	0	0	2 ( 2.8)	1 ( 1.4)	0	0	1 ( 1.0)	0
ARTHRALGIA	1 ( 1.2)	0	0	0	1 ( 1.4)	0	1 ( 1.0)	2 ( 2.1)	0
SHOULDER PAIN	1 ( 1.2)	1 (1.2)	0	0	0	0	2 ( 2.1)	0	0
MUSCLE SPASMS	0	0	0	1 ( 1.4)	0	0	0	0	1 (1.0)
ARTHRITIS	0	0	0	0	1 ( 1.4)	0	0	0	0
FLANK PAIN	0	0	0	0	1 ( 1.4)	0	0	0	0
MUSCULAR WEAKNESS	0	0	0	0	0	0	0	1 ( 1.0)	0
MYALGIA	0	0	0	1 ( 1.4)	0	0	0	0	0
PAIN IN EXTREMITY	1 ( 1.2)	0	0	0	0	0	0	0	0
INJURY, POISONING AND PROCEDURAL COMPLICATIONS	3 ( 3.5)	0	1 (1.2)	2 ( 2.8)	3 ( 4.2)	1 (1.4)	3 ( 3.1)	4 ( 4.2)	0
CONTUSION	1 ( 1.2)	0	0	2 ( 2.8)	0	0	1 ( 1.0)	1 ( 1.0)	0
EXCORIATION	2 ( 2.3)	0	0	0	1 ( 1.4)	0	0	1 ( 1.0)	0
FALL	1 ( 1.2)	0	0	1 ( 1.4)	0	0	1 ( 1.0)	1 ( 1.0)	0
HIP FRACTURE	0	0	1 (1.2)	0	1 ( 1.4)	1 (1.4)	0	0	0
SKIN LACERATION	1 ( 1.2)	0	0	0	0	0	1 ( 1.0)	1 ( 1.0)	0
FACIAL BONES FRACTURE	0	0	0	0	1 ( 1.4)	0	0	0	0
JOINT DISLOCATION	0	0	0	0	0	0	0	1 ( 1.0)	0
WOUND	0	0	0	0	0	0	1 ( 1.0)	0	0
RENAL AND URINARY DISORDERS	3 ( 3.5)	1 (1.2)	0	1 ( 1.4)	2 ( 2.8)	0	3 ( 3.1)	0	0
MICTURITION URGENCY	1 ( 1.2)	0	0	1 ( 1.4)	0	0	1 ( 1.0)	0	0
DYSURIA	1 ( 1.2)	0	0	0	0	0	1 ( 1.0)	0	0
NEPHROLITHIASIS	0	1 (1.2)	0	0	1 ( 1.4)	0	0	0	0
CALCULUS URETHRAL	0	0	0	0	1 ( 1.4)	0	0	0	0
INCONTINENCE	0	0	0	0	0	0	1 ( 1.0)	0	0
POLLAKIURIA	1 ( 1.2)	0	0	0	0	0	0	0	0
METABOLISM AND NUTRITION DISORDERS	5 ( 5.8)	2 (2.3)	0	1 ( 1.4)	1 ( 1.4)	0	0	1 ( 1.0)	0
DECREASED APPETITE	1 ( 1.2)	1 (1.2)	0	0	1 ( 1.4)	0	0	0	0
FOOD CRAVING	1 ( 1.2)	0	0	0	0	0	0	1 ( 1.0)	0
INCREASED APPETITE	1 ( 1.2)	0	0	1 ( 1.4)	0	0	0	0	0
DEHYDRATION	1 ( 1.2)	0	0	0	0	0	0	0	0
DIABETES MELLITUS	1 ( 1.2)	0	0	0	0	0	0	0	0
HYPONATRAEMIA	0	1 (1.2)	0	0	0	0	0	0	0
VASCULAR DISORDERS	2 ( 2.3)	2 (2.3)	0	0	1 ( 1.4)	0	3 ( 3.1)	0	0
HYPOTENSION	2 ( 2.3)	1 (1.2)	0	0	0	0	1 ( 1.0)	0	0
HYPERTENSION	0	1 (1.2)	0	0	0	0	1 ( 1.0)	0	0
HOT FLUSH	0	0	0	0	0	0	1 ( 1.0)	0	0
ORTHOSTATIC HYPOTENSION	1 ( 1.2)	0	0	0	0	0	0	0	0
WOUND HAEMORRHAGE	0	0	0	0	1 ( 1.4)	0	0	0	0
EYE DISORDERS	1 ( 1.2)	1 (1.2)	0	0	1 ( 1.4)	0	1 ( 1.0)	1 ( 1.0)	0
VISION BLURRED	0	0	0	0	1 ( 1.4)	0	1 ( 1.0)	0	0
CONJUNCTIVAL HAEMORRHAGE	0	0	0	0	0	0	0	1 ( 1.0)	0
CONJUNCTIVITIS	0	1 (1.2)	0	0	0	0	0	0	0
EYE ALLERGY	1 ( 1.2)	0	0	0	0	0	0	0	0
EYE PRURITUS	1 ( 1.2)	0	0	0	0	0	0	0	0
EYE SWELLING	1 ( 1.2)	0	0	0	0	0	0	0	0
SURGICAL AND MEDICAL PROCEDURES	1 ( 1.2)	1 (1.2)	0	2 ( 2.8)	0	0	1 ( 1.0)	0	0
CATARACT OPERATION	0	1 (1.2)	0	0	0	0	1 ( 1.0)	0	0
ACROCHORDON EXCISION	0	0	0	1 ( 1.4)	0	0	0	0	0
EYE LASER SURGERY	1 ( 1.2)	0	0	0	0	0	0	0	0
SKIN LESION EXCISION	0	0	0	1 ( 1.4)	0	0	0	0	0
EAR AND LABYRINTH DISORDERS	1 ( 1.2)	0	0	0	1 ( 1.4)	0	1 ( 1.0)	1 ( 1.0)	0
VERTIGO	0	0	0	0	1 ( 1.4)	0	0	1 ( 1.0)	0
CERUMEN IMPACTION	0	0	0	0	0	0	1 ( 1.0)	0	0
EAR PAIN	1 ( 1.2)	0	0	0	0	0	0	0	0
CONGENITAL, FAMILIAL AND GENETIC DISORDERS	0	0	0	2 ( 2.8)	0	0	0	1 ( 1.0)	0
VENTRICULAR SEPTAL DEFECT	0	0	0	2 ( 2.8)	0	0	0	1 ( 1.0)	0
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)	0	0	0	0	0	1 (1.4)	1 ( 1.0)	0	1 (1.0)
COLON CANCER	0	0	0	0	0	0	0	0	1 (1.0)
MALIGNANT FIBROUS HISTIOCYTOMA	0	0	0	0	0	0	1 ( 1.0)	0	0
PROSTATE CANCER	0	0	0	0	0	1 (1.4)	0	0	0
REPRODUCTIVE SYSTEM AND BREAST DISORDERS	2 ( 2.3)	0	1 (1.2)	0	1 ( 1.4)	0	0	0	0
BENIGN PROSTATIC HYPERPLASIA	1 ( 1.2)	0	1 (1.2)	0	1 ( 1.4)	0	0	0	0
PELVIC PAIN	1 ( 1.2)	0	0	0	0	0	0	0	0
HEPATOBILIARY DISORDERS	0	1 (1.2)	0	0	0	0	0	0	0
HYPERBILIRUBINAEMIA	0	1 (1.2)	0	0	0	0	0	0	0
IMMUNE SYSTEM DISORDERS	0	0	0	0	0	0	1 ( 1.0)	0	0
HYPERSENSITIVITY	0	0	0	0	0	0	1 ( 1.0)	0	0
SOCIAL CIRCUMSTANCES	0	0	0	1 ( 1.4)	0	0	0	0	0
ALCOHOL USE	0	0	0	1 ( 1.4)	0	0	0	0	0

TEAE = Treatment-Emergent Adverse Event. Subjects counted once per SOC×grade and once per PT×grade.

Severity grade: MILD, MODERATE, SEVERE as recorded in AESEV.

Percentages based on N per treatment arm (Safety Population).

SOC rows sorted by descending subject frequency; PT rows sorted within SOC by descending frequency.

/opt/quarto/share/rmd/rmd.R 01APR2026 09:52:06