Incidence of treatment-emergent adverse events (AEs) and grade ≥3 laboratory abnormalities (safety (intent-to-treat) population)

AE category24 weeks of bedaquiline treatment
Overall 120 weeks of treatment
Any AE212 (91.0)219 (94.0)
Any serious AE15 (6.4)47 (20.2)
Any AE related to TB47 (20.2)77 (33.0)
Any grade 4 AE5 (2.1)24 (10.3)
Any AE possibly related to bedaquiline77 (33.0)77 (33.0)
Any serious AE possibly related to bedaquiline1 (0.4)1 (0.4)
Any AE leading to bedaquiline discontinuation6 (2.6)#6 (2.6)#
Any AE leading to background regimen discontinuation49 (21.0)73 (31.3)
AEs regardless of causality with >10% incidence
 Hyperuricaemia49 (21.0)56 (24.0)
 Nausea27 (11.6)35 (15.0)
 Arthralgia29 (12.4)35 (15.0)
 Headache21 (9.0)31 (13.3)
 Diarrhoea18 (7.7)27 (11.6)
 Vomiting21 (9.0)27 (11.6)
AEs of special interest
 Hepatic disorders27 (11.6)42 (18.0)
  Increased AST9 (3.9)14 (6.0)
  Increased ALT5 (2.1)12 (5.2)
 QT prolongation+6 (2.6)10 (4.3)
 Severe cutaneous AEs8 (3.4)9 (3.9)§
 Acute pancreatitisƒ3 (1.3)7 (3.0)
Laboratory abnormalities grade ≥3 with >3% incidence  during 120 weeks##N=229N=230
 Hyperuricaemia22 (9.6)29 (12.6)
 Increased AST8 (3.5)20 (8.7)
 Increased γ-glutamyltransferase3 (1.3)12 (5.2)
 Increased leukocytes4 (1.7)10 (4.3)
 Increased ALT5 (2.1)9 (3.9)
 Hyperglycaemia6 (2.6)7 (3.0)
QTcF msN=232N=232
 >450–48027 (11.6)36 (15.5)
 >480–5003 (1.3)5 (2.2)
 >5001 (0.4)2 (0.9)
  • Data are presented as n (%). n: number of patients with AE category; N: number of patients with data; TB: tuberculosis; AST: aspartate aminotransferase; ALT: alanine aminotransferase; QTcF: Fridericia-corrected QT. #: in the six patients, this was due to vomiting, TB, pregnancy, QT prolonged (QTcF 461 ms, change from reference of 11 ms), inadequate control of diabetes and hallucinations; : highlighted due to their potential importance based on nonclinical and clinical data on bedaquiline and identified using the Standardised MedDRA Queries (SMQs) for acute pancreatitis, rhabdomyolysis/myopathy, severe cutaneous AEs and Torsades de Pointes/QT prolongation, and selected sub-SMQs from drug-related hepatic disorders (liver-related investigations, signs and symptoms (SMQ), liver-related coagulation and bleeding disturbances (SMQ) and cholestasis and jaundice of hepatic origin (SMQ), including hepatic failure, fibrosis and cirrhosis and other liver damage-related conditions (SMQ) and hepatitis, noninfectious (SMQ)); +: no incidences of Torsades de Pointes or ventricular arrhythmias were reported; §: in all nine patients who experienced the severe cutaneous SMQ event, this was based upon a preferred term of conjunctivitis (all events were of grade 1 and 2, and two (0.9%) were reported as possibly related to bedaquiline by the investigator); ƒ: in patients who experienced the acute pancreatitis SMQ event, this was based upon investigations (blood amylase increased, blood bilirubin increased), hepatobiliary disorders (hyperbilirubinaemia), and metabolism and nutrition disorders (hyperamylasaemia); ##: includes all laboratory abnormalities not only those reported as an AE.