Table 7.
Summary of 28 deaths from the three Phase 2 studies (among 336 patients allocated to bedaquiline plus OBR, and 105 allocated to OBR alone) [17]
| Number | Days since last intake of BDQ | Phase 2 studya | Treatment arm (bedaquiline + or placebo) | Premature discontinuation/exclusion from treatment | Last culture conversion status | Reported cause of death |
|---|---|---|---|---|---|---|
| 1 | 2 | Second | BDQ | No | Converter | Alcohol poisoning |
| 2 | 12 | Third | BDQ | ns | Non-converter | Renal impairment |
| 3 | 27 | Third | BDQ | ns | Non-converter | Tuberculosis |
| 4 | 45 | Third | BDQ | ns | Non-converter | Tuberculosis |
| 5 | 71 | Third | BDQ | ns | Converter | Lung infection |
| 6 | 86 | Second | BDQ | No | Converter | Hepatitis/hepatic cirrhosis |
| 7 | 105 | Second | Placebo | No | Non-converter | Hemoptysis |
| 8 | 115 | First | BDQ | No | Non-converter | Acute myocardial infarction |
| 9 | 262 | Second | BDQ | Yes (non-compliance) | Relapse | Tuberculosis |
| 10 | 262 | Third | BDQ | ns | Converter | Congestive cardiac failure |
| 11 | 267 | First | Placebo | Yes (exclusion as XDR-TB) | Non-converter | Tuberculosis |
| 12 | 281 | Second | BDQ | No | Relapse | Tuberculosis |
| 13 | 288 | Third | BDQ | ns | Relapse | Tuberculosis |
| 14 | 314 | Second | BDQ | Yes (exclusion as XDR-TB) | Non-converter | Tuberculosis |
| 15 | 344 | Second | BDQ | No | Relapse | Tuberculosis |
| 16 | 427 | First | Placebo | Yes (exclusion as XDR-TB) | Non-converter | Tuberculosis |
| 17 | 463 | Third | BDQ | ns | Non-converter | Tuberculosis |
| 18 | 473 | Third | BDQ | ns | Non-converter | Hypertension |
| 19 | 476 | Third | BDQ | ns | Non-converter | Pyopneumothorax/respiratory failure |
| 20 | 479 | Third | BDQ | ns | Converter | Hemoptysis |
| 21 | 504 | First | BDQ | Yes (exclusion as XDR-TB) | Non-converter | Tuberculosis |
| 22 | 513 | Second | BDQ | No | Converter | Septic shock/peritonitis |
| 23 | 556 | Second | BDQ | No | Converter | Cerebrovascular accident |
| 24 | 632 | Third | BDQ | ns | Converter | Tuberculosis |
| 25 | 685 | Third | BDQ | ns | Non-converter | Cardiac arrest, pneumonia |
| 26 | 709 | Second | Placebo | Yes (non-compliance) | Non-converter | Tuberculosis |
| 27 | 787 | Second | BDQ | Yes (non-compliance) | Non-converter | Tuberculosis |
| 28 | 911 | Second | BDQ | Yes (increased transaminase) | Relapse | Motor vehicle accident |
Source: information from manufacturer’s submission to US FDA [17]. Data for mortality for incomplete trials are given up to the reporting cut-off date specified in the manufacturer’s submission
BDQ bedaquiline, FDA US Food and Drugs Administration, ns not stated, OBR optimized background regimen, XDR-TB extensively drug-resistant tuberculosis
aFirst study: Study C208 (Stage 1); Second study: Study C208 (Stage 2); Third study: Study C209