TABLE 4

Exposure, safety and tolerability during double-blind treatment period

PlaceboBosentan
Patients n174#159
Exposure to double-blind study drug months
 Mean±sd30.7±24.3126.4±20.99
 Median (interquartile range)23.3 (0.3–85.7)22.7 (0.0–86.7)
Variable
 Patients with adverse events159 (91.4)144 (90.6)
 Patients with serious adverse events102 (58.6)73 (45.9)
 Patients with adverse events leading to discontinuation of   double-blind treatment22 (12.6)39 (24.5)
Patients with adverse events
 Worsening of pulmonary arterial hypertension61 (35.1)39 (24.5)
 Oedema, peripheral28 (16.1)30 (18.9)
 Dyspnoea26 (14.9)25 (15.7)
 Headache24 (13.8)24 (15.1)
 Upper respiratory tract infection30 (17.2)22 (13.8)
 Cough21 (12.1)22 (13.8)
 Chest pain16 (9.2)22 (13.8)
 Diarrhoea19 (10.9)19 (11.9)
 Pneumonia13 (7.5)18 (11.3)
 Bronchitis21 (12.1)17 (10.7)
 Dizziness18 (10.3)17 (10.7)
 Anaemia12 (6.9)17 (10.7)
 Nausea22 (12.6)16 (10.1)
 Urinary tract infection14 (8.0)16 (10.1)
 ALT increase8 (4.6)16 (10.1)
 Back pain23 (13.2)15 (9.4)
 Arthralgia20 (11.5)13 (8.2)
 Fatigue20 (11.5)13 (8.2)
 Syncope12 (6.9)8 (5.0)
 Hypotension7 (4.0)0 (0)
Laboratory abnormality
 ALT or AST >3×ULN11 (6.4)34 (21.8)
 ALT or AST >8×ULN0 (0)8 (5.1)
 Haemoglobin ≤10 g·dL−115 (8.8)14 (9.0)
  • Data are presented as n (%) unless otherwise stated. ALT: alanine aminotransferase; AST: aspartate aminotransferase; ULN: upper limit of normal. #: one patient randomly assigned to receive placebo did not receive the study drug and was excluded from the safety analyses. : placebo, n=171; bosentan, n=156.