Table 4.
Safety data *
| DS-TB | RR-TB | |||||
|---|---|---|---|---|---|---|
| Total† (n = 271) n (%) | HRZE (n = 68) n (%) | 4Pa100MZ‡ (n = 65) n (%) | 4Pa200MZ‡ (n = 71) n (%) | 6Pa200MZ‡ (n = 67) n (%) | 6Pa200MZ‡ (n = 13) n (%) | |
| Grade 3+ AEs | ||||||
| On treatment§ | 87 (32.1) | 19 (27.9) | 25 (38.5) | 21 (29.6) | 22 (32.8) | 3 (23.1) |
| Post-treatment | 21 (7.7) | 3 (4.4) | 4 (6.2) | 11 (15.5) | 3 (4.5) | 0 |
| Patients with at least one treatment-emergent AE¶ leading to early discontinuation from study drug | 27 (10.0) | 4 (5.9) | 6 (9.2) | 6 (8.5) | 11 (16.4) | 0 |
| Top 5 treatment-emergent AEs reported for ≥5% patients by preferred term | ||||||
| Hyperuricaemia | 77 (28.4) | 22 (32.4) | 20 (30.8) | 21 (29.6) | 14 (20.9) | 2 (15.4) |
| Arthralgia | 73 (26.9) | 15 (22.1) | 15 (23.1) | 24 (33.8) | 19 (28.4) | 4 (30.1) |
| Aspartate aminotransferase increased | 61 (22.5) | 17 (25.0) | 15 (23.1) | 11 (15.5) | 18 (26.9) | 1 (7.7) |
| ALT increased | 53 (19.6) | 11 (16.2) | 13 (20.0) | 11 (15.5) | 18 (26.9) | 1 (7.7) |
| Blood uric acid increased | 46 (17.0) | 8 (11.8) | 15 (23.1) | 11 (15.5) | 11 (16.4) | 0 (0.0) |
| Patients with ≥1 SAE | 22 (8.1) | 3 (4.4) | 3 (4.6) | 8 (11.3) | 8 (11.9) | 3 (23.1) |
| Liver-related SAEs | 9 (3.3) | 0 (0.0) | 1 (1.5) | 4 (5.6) | 4 (6.0) | 0 (0.0) |
| Peak ALT result | ||||||
| >3xULN | 40 (14.8) | 5 (7.4) | 9 (13.8) | 12 (16.9) | 14 (20.9) | 1 (7.7) |
| >5xULN | 27 (9.9) | 4 (5.9) | 4 (6.2) | 9 (12.6) | 10 (14.9) | 1 (7.7) |
| >10xULN | 16 (5.9) | 2 (2.9) | 4 (6.2) | 5 (7.0) | 5 (7.5) | 1 (7.7) |
| Mean change from baseline in QTcF (95% CI)# | — | 9.2 (5.4–12.9) | 13.3 (10.0–16.6) | 17.6 (13.8–21.5) | 18.3 (15.1–21.5) | 13.7 (2.5–23.8) |
| Deaths | 12 (4.4) | 2 (2.9) | 4 (6.2) | 3 (4.2) | 3 (4.5) | 1 (7.7) |
* All participants who received one or more doses of study drug were included in the safety analysis.
† Includes control arm but does not include the (non-randomised) MDR-TB patients.
‡ 200 mg pretomanid (Pa, PMD) daily, 400 mg moxifloxacin (M) and 1500 mg pyrazinamide (Z) for 6 months (6Pa200MZ) or 4 months (4Pa200MZ); 100 mg pretomanid daily for 4 months in the same combination (4Pa100MZ).
§ Period from first dose of trial drug up to 14 days after last dose.
¶ AEs occurring between first dose of study medication and up to 14 days after last dose.
# Mean change from baseline in QTcB interval across visits for readings taken on or after the first administration of trial drug up to and including 14 days after the last administration of trial drug.
DS-TB = drug-susceptible TB; RR-TB = rifampicin-resistant TB; H = isoniazid; R = rifampicin; Z = pyrazinamide; E = ethambutol; M = moxifloxacin; Pa = pretomanid; AE = adverse event; ALT =alanine aminotransferase; SAE = serious adverse event; ULN = upper limit of normal; CI = confidence interval.