Incidence of treatment-emergent adverse events (AEs) and grade ≥3 laboratory abnormalities (safety (intent-to-treat) population)
| AE category | 24 weeks of bedaquiline treatment N=233 | Overall 120 weeks of treatment N=233 |
| Any AE | 212 (91.0) | 219 (94.0) |
| Any serious AE | 15 (6.4) | 47 (20.2) |
| Any AE related to TB | 47 (20.2) | 77 (33.0) |
| Any grade 4 AE | 5 (2.1) | 24 (10.3) |
| Any AE possibly related to bedaquiline | 77 (33.0) | 77 (33.0) |
| Any serious AE possibly related to bedaquiline | 1 (0.4) | 1 (0.4) |
| Any AE leading to bedaquiline discontinuation | 6 (2.6)# | 6 (2.6)# |
| Any AE leading to background regimen discontinuation | 49 (21.0) | 73 (31.3) |
| AEs regardless of causality with >10% incidence | ||
| Hyperuricaemia | 49 (21.0) | 56 (24.0) |
| Nausea | 27 (11.6) | 35 (15.0) |
| Arthralgia | 29 (12.4) | 35 (15.0) |
| Headache | 21 (9.0) | 31 (13.3) |
| Diarrhoea | 18 (7.7) | 27 (11.6) |
| Vomiting | 21 (9.0) | 27 (11.6) |
| AEs of special interest¶ | ||
| Hepatic disorders | 27 (11.6) | 42 (18.0) |
| Increased AST | 9 (3.9) | 14 (6.0) |
| Increased ALT | 5 (2.1) | 12 (5.2) |
| QT prolongation+ | 6 (2.6) | 10 (4.3) |
| Severe cutaneous AEs | 8 (3.4) | 9 (3.9)§ |
| Acute pancreatitisƒ | 3 (1.3) | 7 (3.0) |
| Laboratory abnormalities grade ≥3 with >3% incidence during 120 weeks## | N=229 | N=230 |
| Hyperuricaemia | 22 (9.6) | 29 (12.6) |
| Increased AST | 8 (3.5) | 20 (8.7) |
| Increased γ-glutamyltransferase | 3 (1.3) | 12 (5.2) |
| Increased leukocytes | 4 (1.7) | 10 (4.3) |
| Increased ALT | 5 (2.1) | 9 (3.9) |
| Hyperglycaemia | 6 (2.6) | 7 (3.0) |
| QTcF ms | N=232 | N=232 |
| >450–480 | 27 (11.6) | 36 (15.5) |
| >480–500 | 3 (1.3) | 5 (2.2) |
| >500 | 1 (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.