Table 4.
Frequency of all NPAEs occurring with tafenoquine/chloroquine versus primaquine/chloroquine (day 1 to day 180) [9–11]
| Event—n (%) patients | Gradea | Integrated safety summary | |
|---|---|---|---|
| Tafenoquine (N = 483) | Primaquine (N = 264) | ||
| Nervous system disorders | Any | 105 (22) | 60 (23) |
| Grade 1 | 78 (16) | 38 (14) | |
| Grade 2 | 26 (5) | 19 (7) | |
| Grade 3 | 0 | 2 (< 1) | |
| NA | 1 (< 1) | 1 (< 1) | |
| Headache | Any | 64 (13) | 40 (15) |
| Grade 1 | 45 (9) | 22 (8) | |
| Grade 2 | 18 (4) | 16 (6) | |
| Grade 3 | 0 | 2 (< 1) | |
| NA | 1 (< 1) | 0 | |
| Dizziness | Any | 59 (12) | 30 (11) |
| Grade 1 | 52 (11) | 25 (9) | |
| Grade 2 | 7 (1) | 4 (2) | |
| NA | 0 | 1 (< 1) | |
| Migraine | Any | 3 (< 1) | 1 (< 1) |
| Grade 1 | 2 (< 1) | 0 | |
| Grade 2 | 1 (< 1) | 1 (< 1) | |
| Syncope | Any | 2 (< 1) | 1 (< 1) |
| Grade 1 | 1 (< 1) | 1 (< 1) | |
| Grade 2 | 1 (< 1) | 0 | |
| Balance disorder | Any | 1 (< 1) | 0 |
| Grade 2 | 1 (< 1) | 0 | |
| Somnolence | Any | 1 (< 1) | 0 |
| Grade 2 | 1 (< 1) | 0 | |
| Tremor | Any | 1 (< 1) | 1 (< 1) |
| Grade 1 | 1 (< 1) | 1 (< 1) | |
| Burning sensation | Any | 0 | 1 (< 1) |
| Grade 1 | 0 | 1 (< 1) | |
| Dysaesthesia | Any | 0 | 1 (< 1) |
| Grade 1 | 0 | 1 (< 1) | |
| Hypoaesthesia | Any | 0 | 1 (< 1) |
| Grade 2 | 0 | 1 (< 1) | |
| Psychiatric disorders | Any | 15 (3) | 12 (5) |
| Grade 1 | 9 (2) | 7 (3) | |
| Grade 2 | 6 (1) | 5 (2) | |
| Insomnia | Any | 15 (3) | 8 (3) |
| Grade 1 | 9 (2) | 4 (2) | |
| Grade 2 | 6 (1) | 4 (2) | |
| Anxiety | Any | 2 (< 1) | 3 (1) |
| Grade 1 | 0 | 2 (< 1) | |
| Grade 2 | 2 (< 1) | 1 (< 1) | |
| Depression | Any | 0 | 1 (< 1) |
| Grade 1 | 0 | 1 (< 1) | |
| Expanded definition of NPAEs | |||
| Asthenia | Any | 8 (2) | 5 (2) |
| Grade 1 | 7 (1) | 2 (< 1) | |
| Grade 2 | 1 (< 1) | 3 (1) | |
| Fatigue | Any | 3 (< 1) | 0 |
| Grade 1 | 3 (< 1) | 0 | |
| Labyrinthitis | Any | 2 (< 1) | 0 |
| Grade 1 | 2 (< 1) | 0 | |
| Alcohol intolerance | Any | 1 (< 1) | 0 |
| Grade 1 | 1 (< 1) | 0 | |
| Vertigo | Any | 3 (< 1) | 1 (< 1) |
| Grade 1 | 2 (< 1) | 1 (< 1) | |
| Grade 2 | 1 (< 1) | 0 | |
| Vestibular disorder | Any | 1 (< 1) | 0 |
| Grade 1 | 1 (< 1) | 0 | |
Data are from the DETECTIVE phase 2b, DETECTIVE phase 3, and GATHER trials (safety population). Vivax malaria patients were treated with chloroquine plus either single-dose tafenoquine 300 mg or primaquine 15 mg for 14 days. Adverse events of Grade 3 and above in any treatment group are italicized
Note that this includes adverse events that were associated with recurrences after day 29. Subjects that experienced recurrence received further treatment with primaquine. Thus, the comparison of adverse events before day 29 provides a more reliable indicator of potential differences caused by drug treatment (see Fig. 4)
aCommon Terminology Criteria for Adverse Events v4.0