Attach multi-level column headers

Build the column-header band(s) above the rendered table. Each named argument is one band; the value is either a character vector of column names (leaf band) or a named list of further bands (inner band). Nesting depth is arbitrary — the engine renders one band row per depth level, with each cell spanning the columns of its leaves.

Usage

headers(.spec, ...)

Arguments

.spec

The tabular_spec to attach the header tree to. <tabular_spec>: required. Dot-prefixed so R's partial argument matching cannot accidentally bind a short user-supplied band label in ... to the spec slot.

...

Named header bands. Each name is the band label (must be non-blank); each value is either:

a character vector of data-column names — leaf band, or
a named list whose entries follow the same recursive pattern — inner band.

Inside a nested-list value, an unnamed character-vector entry declares a passthrough leaf (see the Passthrough section below).

Restriction: Every column referenced must exist in .spec@data. A column may appear under at most one leaf. Names must be unique within one headers() call. Tip: Pass headers() with no arguments to clear the tree. Interaction: Band labels support glue-style {expr} interpolation, evaluated as R code in the calling environment at build time (double a brace for a literal one). The non-blank and uniqueness checks apply to the raw author-typed name, before interpolation.

Value

The updated tabular_spec. Continue chaining with sort_rows(), style().

Details

Replace, not stack. A second headers() call REPLACES the prior tree — header structure is a single spec, not a stackable list. Call with no arguments to clear the tree.

Strict label rule. Every declared band label must carry visible text — empty strings, NA, and whitespace-only labels are rejected at every nesting level. This is stricter than col_spec(), which DOES accept empty labels (a row-label column with no header text is a legitimate clinical case). A silently-blank band would be a layout artefact.

Uncovered columns render naked. Columns not referenced under any band render with their col_spec.label only — no extra band row above them. This is the canonical pattern for row-label columns (variable, soc, stat_label).

Multi-line band labels. Embed \n in a band label for a two-line band cell (arm name on row 1, BigN on row 2).

Spanner underline trim (backend limitation). Each spanner's underline is trimmed at both ends, booktabs \cmidrule(lr) style, so adjacent spanners are separated by a visible gap rather than merging into one continuous line. PDF / LaTeX (tabularray leftpos/rightpos) and HTML (an inset rule) render the trim natively. RTF and DOCX cannot inset a cell border horizontally, so there the spanner underline spans the full band width (adjacent spanner rules abut). This is a known, documented limitation of the OOXML / RTF cell-border model, not a bug.

Passthrough leaves inside a nested band

Inside a nested-list value, a child entry may be unnamed — the entry is then a character vector of column names that sit directly under the parent with no intermediate band at this depth. Use this when one column under a band has no sub-grouping while its siblings do. The strict-label rule still applies to every declared band; an unnamed passthrough is NOT a band with a missing label — it is "no band declared at this depth for this column."

Examples

# ---- Example 1: Single "Treatment Group" band over four arms ----
#
# AE-by-SOC/PT table with one flat band labelled "Treatment Group"
# spanning the four arm columns and the Total column. The
# row-label column (`soc`) sits to the left of the band with no
# header covering it — the canonical clinical layout.
n <- stats::setNames(cdisc_saf_n$n, cdisc_saf_n$arm_short)

tabular(
  cdisc_saf_aesocpt,
  titles = c(
    "Table 14.3.1",
    "Adverse Events by System Organ Class and Preferred Term",
    "Safety Population"
  ),
  footnotes = "Subjects are counted once per SOC and once per PT."
) |>
  cols(
    label    = col_spec(label = "SOC / PT", indent = "indent_level"),
    soc      = col_spec(visible = FALSE),
    row_type = col_spec(visible = FALSE),
    soc_n    = col_spec(visible = FALSE),
    n_total  = col_spec(visible = FALSE),
    placebo  = col_spec(label = "Placebo\nN={n['placebo']}"),
    drug_50  = col_spec(label = "Drug 50\nN={n['drug_50']}"),
    drug_100 = col_spec(label = "Drug 100\nN={n['drug_100']}"),
    Total    = col_spec(label = "Total\nN={n['Total']}")
  ) |>
  headers(
    "Treatment Group" = c("placebo", "drug_50", "drug_100", "Total")
  ) |>
  sort_rows(by = c("soc_n", "n_total"), descending = c(TRUE, TRUE))
 
Table 14.3.1
Adverse Events by System Organ Class and Preferred Term
Safety Population
 

Treatment Group
SOC / PT Placebo
N=86 Drug 50
N=96 Drug 100
N=72 Total
N=254
TOTAL SUBJECTS WITH AN EVENT 52 (60.5) 81 (84.4) 66 (91.7) 199 (78.3)
SKIN AND SUBCUTANEOUS TISSUE DISORDERS 19 (22.1) 36 (37.5) 35 (48.6) 90 (35.4)
PRURITUS 8 (9.3) 21 (21.9) 25 (34.7) 54 (21.3)
ERYTHEMA 8 (9.3) 14 (14.6) 14 (19.4) 36 (14.2)
RASH 5 (5.8) 13 (13.5) 8 (11.1) 26 (10.2)
HYPERHIDROSIS 2 (2.3) 4 (4.2) 8 (11.1) 14 (5.5)
SKIN IRRITATION 3 (3.5) 6 (6.2) 5 (6.9) 14 (5.5)
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS 15 (17.4) 36 (37.5) 30 (41.7) 81 (31.9)
APPLICATION SITE PRURITUS 6 (7.0) 23 (24.0) 21 (29.2) 50 (19.7)
APPLICATION SITE ERYTHEMA 3 (3.5) 13 (13.5) 14 (19.4) 30 (11.8)
APPLICATION SITE DERMATITIS 5 (5.8) 9 (9.4) 7 (9.7) 21 (8.3)
APPLICATION SITE IRRITATION 3 (3.5) 9 (9.4) 9 (12.5) 21 (8.3)
APPLICATION SITE VESICLES 1 (1.2) 5 (5.2) 5 (6.9) 11 (4.3)
GASTROINTESTINAL DISORDERS 13 (15.1) 12 (12.5) 17 (23.6) 42 (16.5)
DIARRHOEA 9 (10.5) 5 (5.2) 3 (4.2) 17 (6.7)
VOMITING 3 (3.5) 4 (4.2) 6 (8.3) 13 (5.1)
NAUSEA 3 (3.5) 3 (3.1) 6 (8.3) 12 (4.7)
ABDOMINAL PAIN 1 (1.2) 3 (3.1) 1 (1.4) 5 (2.0)
SALIVARY HYPERSECRETION 0 (0.0) 0 (0.0) 4 (5.6) 4 (1.6)
NERVOUS SYSTEM DISORDERS 6 (7.0) 18 (18.8) 17 (23.6) 41 (16.1)
DIZZINESS 2 (2.3) 9 (9.4) 10 (13.9) 21 (8.3)
HEADACHE 3 (3.5) 3 (3.1) 5 (6.9) 11 (4.3)
SYNCOPE 0 (0.0) 5 (5.2) 2 (2.8) 7 (2.8)
SOMNOLENCE 2 (2.3) 3 (3.1) 1 (1.4) 6 (2.4)
TRANSIENT ISCHAEMIC ATTACK 0 (0.0) 2 (2.1) 1 (1.4) 3 (1.2)
CARDIAC DISORDERS 7 (8.1) 12 (12.5) 14 (19.4) 33 (13.0)
SINUS BRADYCARDIA 2 (2.3) 7 (7.3) 8 (11.1) 17 (6.7)
MYOCARDIAL INFARCTION 4 (4.7) 2 (2.1) 4 (5.6) 10 (3.9)
ATRIAL FIBRILLATION 1 (1.2) 2 (2.1) 2 (2.8) 5 (2.0)
SUPRAVENTRICULAR EXTRASYSTOLES 1 (1.2) 1 (1.0) 1 (1.4) 3 (1.2)
VENTRICULAR EXTRASYSTOLES 0 (0.0) 2 (2.1) 1 (1.4) 3 (1.2)
INFECTIONS AND INFESTATIONS 12 (14.0) 6 (6.2) 11 (15.3) 29 (11.4)
NASOPHARYNGITIS 2 (2.3) 4 (4.2) 6 (8.3) 12 (4.7)
UPPER RESPIRATORY TRACT INFECTION 6 (7.0) 1 (1.0) 3 (4.2) 10 (3.9)
INFLUENZA 1 (1.2) 1 (1.0) 1 (1.4) 3 (1.2)
URINARY TRACT INFECTION 2 (2.3) 0 (0.0) 1 (1.4) 3 (1.2)
CYSTITIS 1 (1.2) 0 (0.0) 1 (1.4) 2 (0.8)
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS 5 (5.8) 8 (8.3) 9 (12.5) 22 (8.7)
COUGH 1 (1.2) 5 (5.2) 5 (6.9) 11 (4.3)
NASAL CONGESTION 3 (3.5) 1 (1.0) 3 (4.2) 7 (2.8)
DYSPNOEA 1 (1.2) 1 (1.0) 1 (1.4) 3 (1.2)
EPISTAXIS 0 (0.0) 1 (1.0) 2 (2.8) 3 (1.2)
PHARYNGOLARYNGEAL PAIN 0 (0.0) 1 (1.0) 1 (1.4) 2 (0.8)
PSYCHIATRIC DISORDERS 7 (8.1) 9 (9.4) 3 (4.2) 19 (7.5)
CONFUSIONAL STATE 2 (2.3) 3 (3.1) 1 (1.4) 6 (2.4)
AGITATION 2 (2.3) 3 (3.1) 0 (0.0) 5 (2.0)
INSOMNIA 2 (2.3) 0 (0.0) 2 (2.8) 4 (1.6)
ANXIETY 0 (0.0) 3 (3.1) 0 (0.0) 3 (1.2)
DELUSION 1 (1.2) 0 (0.0) 1 (1.4) 2 (0.8)
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS 3 (3.5) 6 (6.2) 5 (6.9) 14 (5.5)
BACK PAIN 1 (1.2) 1 (1.0) 3 (4.2) 5 (2.0)
ARTHRALGIA 1 (1.2) 2 (2.1) 1 (1.4) 4 (1.6)
SHOULDER PAIN 1 (1.2) 2 (2.1) 0 (0.0) 3 (1.2)
MUSCLE SPASMS 0 (0.0) 1 (1.0) 1 (1.4) 2 (0.8)
ARTHRITIS 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.4)
INVESTIGATIONS 5 (5.8) 4 (4.2) 3 (4.2) 12 (4.7)
ELECTROCARDIOGRAM ST SEGMENT DEPRESSION 4 (4.7) 1 (1.0) 0 (0.0) 5 (2.0)
ELECTROCARDIOGRAM T WAVE INVERSION 2 (2.3) 1 (1.0) 1 (1.4) 4 (1.6)
BLOOD GLUCOSE INCREASED 0 (0.0) 1 (1.0) 1 (1.4) 2 (0.8)
ELECTROCARDIOGRAM T WAVE AMPLITUDE DECREASED 1 (1.2) 1 (1.0) 0 (0.0) 2 (0.8)
BIOPSY 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.4)
Subjects are counted once per SOC and once per PT.

# ---- Example 2: Two-level nested band — Control vs Active arms ----
#
# Efficacy BOR table where the active arms are grouped under an
# "Active" sub-band and the placebo arm under a "Control"
# sub-band, both under a single "Treatment Group" parent.
# Demonstrates the named-list value form for arbitrary-depth
# nesting.
bor_levels <- c(
  "CR", "PR", "SD", "NON-CR/NON-PD", "PD", "NE", "MISSING",
  "ORR (CR + PR)", "CBR (CR + PR + SD)",
  "DCR (CR + PR + SD + NON-CR/NON-PD)", "95% CI (Clopper-Pearson)"
)
eff <- cdisc_eff_resp
eff$stat_label <- factor(eff$stat_label, levels = bor_levels)
ne <- stats::setNames(cdisc_eff_n$n, cdisc_eff_n$arm_short)

tabular(
  eff,
  titles = c(
    "Table 14.2.1",
    "Best Overall Response and Response Rates",
    "Efficacy Evaluable Population"
  ),
  footnotes = "Response per RECIST 1.1, investigator assessment."
) |>
  cols(
    stat_label  = col_spec(label = "Response"),
    row_type    = col_spec(visible = FALSE),
    groupid     = col_spec(visible = FALSE),
    group_label = col_spec(visible = FALSE),
    placebo    = col_spec(label = "Placebo\nN={ne['placebo']}"),
    drug_50    = col_spec(label = "Drug 50\nN={ne['drug_50']}"),
    drug_100   = col_spec(label = "Drug 100\nN={ne['drug_100']}")
  ) |>
  headers(
    "Treatment Group" = list(
      "Control" = "placebo",
      "Active"  = c("drug_50", "drug_100")
    )
  ) |>
  sort_rows(by = c("groupid", "stat_label"))
 
Table 14.2.1
Best Overall Response and Response Rates
Efficacy Evaluable Population
 

Treatment Group
Control Active
Response Placebo
N=86 Drug 50
N=84 Drug 100
N=84
CR 1 (1.2) 1 (1.2) 1 (1.2)
PR 1 (1.2) 0 0
SD 1 (1.2) 0 0
NON-CR/NON-PD 0 0 1 (1.2)
PD 0 0 1 (1.2)
NE 0 1 (1.2) 0
MISSING 83 (96.5) 82 (97.6) 81 (96.4)
ORR (CR + PR) 2 (2.3) 1 (1.2) 1 (1.2)
95% CI (Clopper-Pearson) (0.3, 8.1) (0.0, 6.5) (0.0, 6.5)
CBR (CR + PR + SD) 3 (3.5) 1 (1.2) 1 (1.2)
95% CI (Clopper-Pearson) (0.7, 9.9) (0.0, 6.5) (0.0, 6.5)
DCR (CR + PR + SD + NON-CR/NON-PD) 3 (3.5) 1 (1.2) 2 (2.4)
95% CI (Clopper-Pearson) (0.7, 9.9) (0.0, 6.5) (0.3, 8.3)
Response per RECIST 1.1, investigator assessment.

# ---- Example 3: Multiple peer bands side by side ----
#
# Vital-signs summary where the parameter columns (param,
# paramcd, visit, stat_label) sit on the left under a "Variable"
# band, and the arm columns sit on the right under "Treatment
# Group". Demonstrates multiple top-level bands in one call --
# bands render side by side in the order declared.
vit <- cdisc_saf_vital
tabular(vit, titles = c("Table 14.4.1", "Vital Signs Summary")) |>
  cols(
    param      = col_spec(usage = "group", label = "Parameter"),
    paramcd    = col_spec(visible = FALSE),
    visit      = col_spec(usage = "group", label = "Visit"),
    stat_label = col_spec(label = "Statistic"),
    placebo    = col_spec(label = "Placebo",  align = "decimal"),
    drug_50    = col_spec(label = "Drug 50",  align = "decimal"),
    drug_100   = col_spec(label = "Drug 100", align = "decimal")
  ) |>
  headers(
    "Variable"        = c("param", "paramcd", "visit", "stat_label"),
    "Treatment Group" = c("placebo", "drug_50", "drug_100")
  )
 
Table 14.4.1
Vital Signs Summary
 

Variable Treatment Group
Statistic Placebo Drug 50 Drug 100
Diastolic Blood Pressure (mmHg)
Baseline
n 340          384          288         
Mean (SD)  77.1 (10.7)  76.6 (9.8)   78.2 (10.3)
Median  77.7         76.7         78.8       
Min, Max  40  , 110    48  , 108    51  , 108  
 
Week 8
n 292          240          224         
Mean (SD)  75.2 (9.1)   75.4 (10.6)  77.4 (9.1) 
Median  76.0         74.0         78.3       
Min, Max  49  , 101    52  , 100    54  , 98   
 
Week 16
n 272          168          148         
Mean (SD)  75.1 (10.9)  75.2 (10.0)  76.0 (9.0) 
Median  76.0         75.7         77.3       
Min, Max  49  , 98     55  , 98     50  , 92   
 
End of Treatment
n 222          177          168         
Mean (SD)  74.4 (10.7)  76.0 (11.2)  76.0 (9.9) 
Median  73.5         76.0         78.0       
Min, Max  49  , 104    50  , 100    56  , 98   
 
Pulse Rate (beats/min)
Baseline
n 340          384          288         
Mean (SD)  73.5 (11.6)  72.1 (10.8)  72.4 (9.7) 
Median  72.3         70.0         71.7       
Min, Max  51  , 134    50  , 104    52  , 100  
 
Week 8
n 292          240          224         
Mean (SD)  71.8 (9.0)   72.6 (11.1)  74.0 (8.9) 
Median  72.0         72.0         73.2       
Min, Max  52  , 102    49  , 104    50  , 104  
 
Week 16
n 272          168          148         
Mean (SD)  70.6 (8.8)   68.8 (9.4)   73.2 (9.5) 
Median  70.2         68.0         72.0       
Min, Max  50  , 90     48  , 104    51  , 96   
 
End of Treatment
n 222          177          168         
Mean (SD)  75.2 (11.5)  74.1 (9.4)   73.6 (9.6) 
Median  74.0         75.0         73.0       
Min, Max  51  , 106    50  , 94     50  , 98   
 
Systolic Blood Pressure (mmHg)
Baseline
n 340          384          288         
Mean (SD) 136.8 (17.6) 137.9 (18.5) 137.8 (17.2)
Median 136.3        138.0        138.0       
Min, Max  80  , 184   100  , 194   100  , 192  
 
Week 8
n 292          240          224         
Mean (SD) 136.3 (17.0) 134.9 (17.8) 135.1 (15.5)
Median 136.5        132.3        134.0       
Min, Max  90  , 189    92  , 200    91  , 198  
 
Week 16
n 272          168          148         
Mean (SD) 134.6 (18.3) 132.5 (14.3) 133.7 (16.0)
Median 134.0        130.0        132.0       
Min, Max  76  , 190   100  , 168    99  , 186  
 
End of Treatment
n 222          177          168         
Mean (SD) 132.7 (15.4) 133.0 (17.1) 132.3 (15.6)
Median 131.0        130.0        131.0       
Min, Max  78  , 172    92  , 178   100  , 177  
 
Temperature (C)
Baseline
n 172          190          144         
Mean (SD)  36.6 (0.4)   36.5 (0.4)   36.6 (0.4) 
Median  36.7         36.6         36.6       
Min, Max  35  , 37     35  , 37     36  , 37   
 
Week 8
n 146          118          112         
Mean (SD)  36.6 (0.4)   36.6 (0.4)   36.6 (0.4) 
Median  36.6         36.7         36.7       
Min, Max  36  , 37     36  , 37     36  , 37   
 
Week 16
n 136           82           74         
Mean (SD)  36.7 (0.3)   36.6 (0.4)   36.6 (0.4) 
Median  36.7         36.6         36.7       
Min, Max  36  , 37     36  , 37     36  , 37   
 
End of Treatment
n  74           59           56         
Mean (SD)  36.7 (0.4)   36.6 (0.4)   36.6 (0.4) 
Median  36.8         36.7         36.7       
Min, Max  35  , 37     35  , 38     36  , 37   

# ---- Example 4: Three-tier band over efficacy arms + Total ----
#
# Demographics-style three-tier nesting: top band labels the
# whole arm strip, middle band splits Active vs Placebo, leaf
# bands carry the per-arm column labels. Each child within a
# `list(...)` may itself be a `list(...)` — bands nest to
# arbitrary depth using nested list literals.
n <- stats::setNames(cdisc_saf_n$n, cdisc_saf_n$arm_short)
tabular(cdisc_saf_demo, titles = "Demographics, hierarchical headers") |>
  cols(
    variable   = col_spec(usage = "group", label = "Characteristic"),
    stat_label = col_spec(label = "Statistic"),
    placebo    = col_spec(label = "N={n['placebo']}"),
    drug_50    = col_spec(label = "N={n['drug_50']}"),
    drug_100   = col_spec(label = "N={n['drug_100']}"),
    Total      = col_spec(label = "N={n['Total']}")
  ) |>
  headers(
    "Treatment Group" = list(
      "Control" = "placebo",
      "Active"  = list(
        "Drug 50"  = "drug_50",
        "Drug 100" = "drug_100"
      ),
      "Pooled"  = "Total"
    )
  )
 
Demographics, hierarchical headers
 

Treatment Group
Control Active Pooled
Drug 50 Drug 100 
Statistic N=86 N=96 N=72 N=254
Age (years)
n 86 96 72 254
Mean (SD) 75.2 (8.59) 76.0 (8.11) 73.8 (7.94) 75.1 (8.25)
Median 76.0 78.0 75.5 77.0
Q1, Q3 69.2, 81.8 71.0, 82.0 70.5, 79.0 70.0, 81.0
Min, Max 52, 89 51, 88 56, 88 51, 89
 
Sex, n (%)
F 53 (61.6) 55 (57.3) 35 (48.6) 143 (56.3)
M 33 (38.4) 41 (42.7) 37 (51.4) 111 (43.7)
 
Race, n (%)
WHITE 78 (90.7) 90 (93.8) 62 (86.1) 230 (90.6)
BLACK OR AFRICAN AMERICAN 8 (9.3) 6 (6.2) 9 (12.5) 23 (9.1)
ASIAN 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)
AMERICAN INDIAN OR ALASKA NATIVE 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.4)

	Treatment Group
SOC / PT	Placebo N=86	Drug 50 N=96	Drug 100 N=72	Total N=254
TOTAL SUBJECTS WITH AN EVENT	52 (60.5)	81 (84.4)	66 (91.7)	199 (78.3)
SKIN AND SUBCUTANEOUS TISSUE DISORDERS	19 (22.1)	36 (37.5)	35 (48.6)	90 (35.4)
PRURITUS	8 (9.3)	21 (21.9)	25 (34.7)	54 (21.3)
ERYTHEMA	8 (9.3)	14 (14.6)	14 (19.4)	36 (14.2)
RASH	5 (5.8)	13 (13.5)	8 (11.1)	26 (10.2)
HYPERHIDROSIS	2 (2.3)	4 (4.2)	8 (11.1)	14 (5.5)
SKIN IRRITATION	3 (3.5)	6 (6.2)	5 (6.9)	14 (5.5)
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS	15 (17.4)	36 (37.5)	30 (41.7)	81 (31.9)
APPLICATION SITE PRURITUS	6 (7.0)	23 (24.0)	21 (29.2)	50 (19.7)
APPLICATION SITE ERYTHEMA	3 (3.5)	13 (13.5)	14 (19.4)	30 (11.8)
APPLICATION SITE DERMATITIS	5 (5.8)	9 (9.4)	7 (9.7)	21 (8.3)
APPLICATION SITE IRRITATION	3 (3.5)	9 (9.4)	9 (12.5)	21 (8.3)
APPLICATION SITE VESICLES	1 (1.2)	5 (5.2)	5 (6.9)	11 (4.3)
GASTROINTESTINAL DISORDERS	13 (15.1)	12 (12.5)	17 (23.6)	42 (16.5)
DIARRHOEA	9 (10.5)	5 (5.2)	3 (4.2)	17 (6.7)
VOMITING	3 (3.5)	4 (4.2)	6 (8.3)	13 (5.1)
NAUSEA	3 (3.5)	3 (3.1)	6 (8.3)	12 (4.7)
ABDOMINAL PAIN	1 (1.2)	3 (3.1)	1 (1.4)	5 (2.0)
SALIVARY HYPERSECRETION	0 (0.0)	0 (0.0)	4 (5.6)	4 (1.6)
NERVOUS SYSTEM DISORDERS	6 (7.0)	18 (18.8)	17 (23.6)	41 (16.1)
DIZZINESS	2 (2.3)	9 (9.4)	10 (13.9)	21 (8.3)
HEADACHE	3 (3.5)	3 (3.1)	5 (6.9)	11 (4.3)
SYNCOPE	0 (0.0)	5 (5.2)	2 (2.8)	7 (2.8)
SOMNOLENCE	2 (2.3)	3 (3.1)	1 (1.4)	6 (2.4)
TRANSIENT ISCHAEMIC ATTACK	0 (0.0)	2 (2.1)	1 (1.4)	3 (1.2)
CARDIAC DISORDERS	7 (8.1)	12 (12.5)	14 (19.4)	33 (13.0)
SINUS BRADYCARDIA	2 (2.3)	7 (7.3)	8 (11.1)	17 (6.7)

MYOCARDIAL INFARCTION	4 (4.7)	2 (2.1)	4 (5.6)	10 (3.9)
ATRIAL FIBRILLATION	1 (1.2)	2 (2.1)	2 (2.8)	5 (2.0)
SUPRAVENTRICULAR EXTRASYSTOLES	1 (1.2)	1 (1.0)	1 (1.4)	3 (1.2)
VENTRICULAR EXTRASYSTOLES	0 (0.0)	2 (2.1)	1 (1.4)	3 (1.2)
INFECTIONS AND INFESTATIONS	12 (14.0)	6 (6.2)	11 (15.3)	29 (11.4)
NASOPHARYNGITIS	2 (2.3)	4 (4.2)	6 (8.3)	12 (4.7)
UPPER RESPIRATORY TRACT INFECTION	6 (7.0)	1 (1.0)	3 (4.2)	10 (3.9)
INFLUENZA	1 (1.2)	1 (1.0)	1 (1.4)	3 (1.2)
URINARY TRACT INFECTION	2 (2.3)	0 (0.0)	1 (1.4)	3 (1.2)
CYSTITIS	1 (1.2)	0 (0.0)	1 (1.4)	2 (0.8)
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS	5 (5.8)	8 (8.3)	9 (12.5)	22 (8.7)
COUGH	1 (1.2)	5 (5.2)	5 (6.9)	11 (4.3)
NASAL CONGESTION	3 (3.5)	1 (1.0)	3 (4.2)	7 (2.8)
DYSPNOEA	1 (1.2)	1 (1.0)	1 (1.4)	3 (1.2)
EPISTAXIS	0 (0.0)	1 (1.0)	2 (2.8)	3 (1.2)
PHARYNGOLARYNGEAL PAIN	0 (0.0)	1 (1.0)	1 (1.4)	2 (0.8)
PSYCHIATRIC DISORDERS	7 (8.1)	9 (9.4)	3 (4.2)	19 (7.5)
CONFUSIONAL STATE	2 (2.3)	3 (3.1)	1 (1.4)	6 (2.4)
AGITATION	2 (2.3)	3 (3.1)	0 (0.0)	5 (2.0)
INSOMNIA	2 (2.3)	0 (0.0)	2 (2.8)	4 (1.6)
ANXIETY	0 (0.0)	3 (3.1)	0 (0.0)	3 (1.2)
DELUSION	1 (1.2)	0 (0.0)	1 (1.4)	2 (0.8)
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS	3 (3.5)	6 (6.2)	5 (6.9)	14 (5.5)
BACK PAIN	1 (1.2)	1 (1.0)	3 (4.2)	5 (2.0)
ARTHRALGIA	1 (1.2)	2 (2.1)	1 (1.4)	4 (1.6)
SHOULDER PAIN	1 (1.2)	2 (2.1)	0 (0.0)	3 (1.2)
MUSCLE SPASMS	0 (0.0)	1 (1.0)	1 (1.4)	2 (0.8)

ARTHRITIS	0 (0.0)	0 (0.0)	1 (1.4)	1 (0.4)
INVESTIGATIONS	5 (5.8)	4 (4.2)	3 (4.2)	12 (4.7)
ELECTROCARDIOGRAM ST SEGMENT DEPRESSION	4 (4.7)	1 (1.0)	0 (0.0)	5 (2.0)
ELECTROCARDIOGRAM T WAVE INVERSION	2 (2.3)	1 (1.0)	1 (1.4)	4 (1.6)
BLOOD GLUCOSE INCREASED	0 (0.0)	1 (1.0)	1 (1.4)	2 (0.8)
ELECTROCARDIOGRAM T WAVE AMPLITUDE DECREASED	1 (1.2)	1 (1.0)	0 (0.0)	2 (0.8)
BIOPSY	0 (0.0)	0 (0.0)	1 (1.4)	1 (0.4)

	Treatment Group
	Control	Active
Response	Placebo N=86	Drug 50 N=84	Drug 100 N=84
CR	1 (1.2)	1 (1.2)	1 (1.2)
PR	1 (1.2)	0	0
SD	1 (1.2)	0	0
NON-CR/NON-PD	0	0	1 (1.2)
PD	0	0	1 (1.2)
NE	0	1 (1.2)	0
MISSING	83 (96.5)	82 (97.6)	81 (96.4)
ORR (CR + PR)	2 (2.3)	1 (1.2)	1 (1.2)
95% CI (Clopper-Pearson)	(0.3, 8.1)	(0.0, 6.5)	(0.0, 6.5)
CBR (CR + PR + SD)	3 (3.5)	1 (1.2)	1 (1.2)
95% CI (Clopper-Pearson)	(0.7, 9.9)	(0.0, 6.5)	(0.0, 6.5)
DCR (CR + PR + SD + NON-CR/NON-PD)	3 (3.5)	1 (1.2)	2 (2.4)
95% CI (Clopper-Pearson)	(0.7, 9.9)	(0.0, 6.5)	(0.3, 8.3)

Variable	Treatment Group
Statistic	Placebo	Drug 50	Drug 100
Diastolic Blood Pressure (mmHg)
Baseline
n	340	384	288
Mean (SD)	77.1 (10.7)	76.6 (9.8)	78.2 (10.3)
Median	77.7	76.7	78.8
Min, Max	40 , 110	48 , 108	51 , 108

Week 8
n	292	240	224
Mean (SD)	75.2 (9.1)	75.4 (10.6)	77.4 (9.1)
Median	76.0	74.0	78.3
Min, Max	49 , 101	52 , 100	54 , 98

Week 16
n	272	168	148
Mean (SD)	75.1 (10.9)	75.2 (10.0)	76.0 (9.0)
Median	76.0	75.7	77.3
Min, Max	49 , 98	55 , 98	50 , 92

End of Treatment
n	222	177	168
Mean (SD)	74.4 (10.7)	76.0 (11.2)	76.0 (9.9)
Median	73.5	76.0	78.0
Min, Max	49 , 104	50 , 100	56 , 98

Pulse Rate (beats/min)
Baseline
n	340	384	288
Mean (SD)	73.5 (11.6)	72.1 (10.8)	72.4 (9.7)
Median	72.3	70.0	71.7
Min, Max	51 , 134	50 , 104	52 , 100

Week 8
n	292	240	224
Mean (SD)	71.8 (9.0)	72.6 (11.1)	74.0 (8.9)
Median	72.0	72.0	73.2
Min, Max	52 , 102	49 , 104	50 , 104

Week 16
n	272	168	148
Mean (SD)	70.6 (8.8)	68.8 (9.4)	73.2 (9.5)
Median	70.2	68.0	72.0
Min, Max	50 , 90	48 , 104	51 , 96

End of Treatment
n	222	177	168
Mean (SD)	75.2 (11.5)	74.1 (9.4)	73.6 (9.6)
Median	74.0	75.0	73.0

Min, Max	51 , 106	50 , 94	50 , 98

Systolic Blood Pressure (mmHg)
Baseline
n	340	384	288
Mean (SD)	136.8 (17.6)	137.9 (18.5)	137.8 (17.2)
Median	136.3	138.0	138.0
Min, Max	80 , 184	100 , 194	100 , 192

Week 8
n	292	240	224
Mean (SD)	136.3 (17.0)	134.9 (17.8)	135.1 (15.5)
Median	136.5	132.3	134.0
Min, Max	90 , 189	92 , 200	91 , 198

Week 16
n	272	168	148
Mean (SD)	134.6 (18.3)	132.5 (14.3)	133.7 (16.0)
Median	134.0	130.0	132.0
Min, Max	76 , 190	100 , 168	99 , 186

End of Treatment
n	222	177	168
Mean (SD)	132.7 (15.4)	133.0 (17.1)	132.3 (15.6)
Median	131.0	130.0	131.0
Min, Max	78 , 172	92 , 178	100 , 177

Temperature (C)
Baseline
n	172	190	144
Mean (SD)	36.6 (0.4)	36.5 (0.4)	36.6 (0.4)
Median	36.7	36.6	36.6
Min, Max	35 , 37	35 , 37	36 , 37

Week 8
n	146	118	112
Mean (SD)	36.6 (0.4)	36.6 (0.4)	36.6 (0.4)
Median	36.6	36.7	36.7
Min, Max	36 , 37	36 , 37	36 , 37

Week 16
n	136	82	74
Mean (SD)	36.7 (0.3)	36.6 (0.4)	36.6 (0.4)
Median	36.7	36.6	36.7
Min, Max	36 , 37	36 , 37	36 , 37

End of Treatment
n	74	59	56
Mean (SD)	36.7 (0.4)	36.6 (0.4)	36.6 (0.4)

Median	36.8	36.7	36.7
Min, Max	35 , 37	35 , 38	36 , 37

	Treatment Group
	Control	Active		Pooled
		Drug 50	Drug 100
Statistic	N=86	N=96	N=72	N=254
Age (years)
n	86	96	72	254
Mean (SD)	75.2 (8.59)	76.0 (8.11)	73.8 (7.94)	75.1 (8.25)
Median	76.0	78.0	75.5	77.0
Q1, Q3	69.2, 81.8	71.0, 82.0	70.5, 79.0	70.0, 81.0
Min, Max	52, 89	51, 88	56, 88	51, 89

Sex, n (%)
F	53 (61.6)	55 (57.3)	35 (48.6)	143 (56.3)
M	33 (38.4)	41 (42.7)	37 (51.4)	111 (43.7)

Race, n (%)
WHITE	78 (90.7)	90 (93.8)	62 (86.1)	230 (90.6)
BLACK OR AFRICAN AMERICAN	8 (9.3)	6 (6.2)	9 (12.5)	23 (9.1)
ASIAN	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
AMERICAN INDIAN OR ALASKA NATIVE	0 (0.0)	0 (0.0)	1 (1.4)	1 (0.4)