TRAEs of interest and other commonly reported nonhematologic TRAEs
| Patients∗, n (%) . | IM 25 mg/m2 MWF (n = 33) . | IM 37.5 mg/m2 MWF (n = 83) . | IM 25/25/50 mg/m2 MWF (n = 51) . | IM total (n = 167) . | IV 25/25/50 mg/m2 MWF (n = 61) . | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| All grades . | Grade 3/4 . | All grades . | Grade 3/4 . | All grades . | Grade 3/4 . | All grades . | Grade 3/4 . | All grades . | Grade 3/4 . | |
| TRAEs of interest | ||||||||||
| Allergic reactions | 2 (6) | 2 (6) | 11 (13) | 6 (7) | 5 (10) | 2 (4) | 18 (11) | 10 (6) | 16 (26) | 11 (18) |
| Hypersensitivity† | 2 (6) | 2 (6) | 6 (7) | 3 (4) | 2 (4) | 2 (4) | 10 (6) | 7 (4) | 11 (18) | 7 (11) |
| Anaphylactic reaction | 0 | 0 | 3 (4) | 3 (4) | 0 | 0 | 3 (2) | 3 (2) | 1 (2) | 1 (2) |
| Rash‡ | 0 | 0 | 3 (4) | 0 | 3 (6) | 0 | 6 (4) | 0 | 0 | 0 |
| Urticaria | 0 | 0 | 0 | 0 | 1 (2) | 0 | 1 (1) | 0 | 1 (2) | 0 |
| Infusion-related reaction | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 (7) | 2 (3) |
| Pancreatitis§ | 0 | 0 | 6 (7) | 6 (7) | 6 (12) | 4 (8) | 12 (7) | 10 (6) | 3 (5) | 2 (3) |
| Thrombosis | 0 | 0 | 2 (2) | 2 (2) | 0 | 0 | 2 (1) | 2 (1) | 1 (2) | 0 |
| SSS thrombosis | 0 | 0 | 1 (1) | 1 (1) | 0 | 0 | 1 (1) | 1 (1) | 0 | 0 |
| Pulmonary embolism | 0 | 0 | 2 (2) | 2 (2) | 0 | 0 | 2 (1) | 2 (1) | 0 | 0 |
| Jugular vein thrombosis | 0 | 0 | 1 (1) | 0 | 0 | 0 | 1 (1) | 0 | 0 | 0 |
| Deep vein thrombosis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (2) | 0 |
| Increased ALT | 2 (6) | 2 (6) | 14 (17) | 8 (10) | 8 (16) | 3 (6) | 24 (14) | 13 (8) | 11 (18) | 7 (11) |
| Increased AST | 2 (6) | 0 | 12 (14) | 4 (5) | 4 (8) | 0 | 18 (11) | 4 (2) | 6 (10) | 3 (5) |
| Increased blood bilirubin‖ | 0 | 0 | 8 (10) | 1 (1) | 3 (6) | 2 (4) | 11 (7) | 3 (2) | 3 (5) | 1 (2) |
| Hyperammonemia | 0 | 0 | 3 (4) | 2 (2) | 0 | 0 | 3 (2) | 2 (1) | 2 (3) | 1 (2) |
| Other commonly reported nonhematologic TRAEs | ||||||||||
| Nausea | 7 (21) | 1 (3) | 20 (24) | 6 (7) | 13 (25) | 2 (4) | 40 (24) | 9 (5) | 27 (44) | 7 (11) |
| Vomiting | 7 (21) | 0 | 22 (27) | 3 (4) | 10 (20) | 1 (2) | 39 (23) | 4 (2) | 36 (59) | 8 (13) |
| Decreased appetite | 3 (9) | 1 (3) | 12 (14) | 3 (4) | 9 (18) | 1 (2) | 24 (14) | 5 (3) | 5 (8) | 0 |
| Fatigue | 3 (9) | 1 (3) | 17 (20) | 0 | 3 (6) | 0 | 23 (14) | 1 (1) | 8 (13) | 0 |
| Febrile neutropenia | 2 (6) | 2 (6) | 11 (13) | 11 (13) | 4 (8) | 4 (8) | 17 (10) | 17 (10) | 3 (5) | 3 (5) |
| Abdominal pain | 2 (6) | 0 | 9 (11) | 2 (2) | 6 (12) | 0 | 17 (10) | 2 (1) | 3 (5) | 1 (2) |
| Hyperglycemia | 3 (9) | 1 (3) | 5 (6) | 2 (2) | 7 (14) | 3 (6) | 15 (9) | 6 (4) | 7 (11) | 6 (10) |
| Patients∗, n (%) . | IM 25 mg/m2 MWF (n = 33) . | IM 37.5 mg/m2 MWF (n = 83) . | IM 25/25/50 mg/m2 MWF (n = 51) . | IM total (n = 167) . | IV 25/25/50 mg/m2 MWF (n = 61) . | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| All grades . | Grade 3/4 . | All grades . | Grade 3/4 . | All grades . | Grade 3/4 . | All grades . | Grade 3/4 . | All grades . | Grade 3/4 . | |
| TRAEs of interest | ||||||||||
| Allergic reactions | 2 (6) | 2 (6) | 11 (13) | 6 (7) | 5 (10) | 2 (4) | 18 (11) | 10 (6) | 16 (26) | 11 (18) |
| Hypersensitivity† | 2 (6) | 2 (6) | 6 (7) | 3 (4) | 2 (4) | 2 (4) | 10 (6) | 7 (4) | 11 (18) | 7 (11) |
| Anaphylactic reaction | 0 | 0 | 3 (4) | 3 (4) | 0 | 0 | 3 (2) | 3 (2) | 1 (2) | 1 (2) |
| Rash‡ | 0 | 0 | 3 (4) | 0 | 3 (6) | 0 | 6 (4) | 0 | 0 | 0 |
| Urticaria | 0 | 0 | 0 | 0 | 1 (2) | 0 | 1 (1) | 0 | 1 (2) | 0 |
| Infusion-related reaction | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 (7) | 2 (3) |
| Pancreatitis§ | 0 | 0 | 6 (7) | 6 (7) | 6 (12) | 4 (8) | 12 (7) | 10 (6) | 3 (5) | 2 (3) |
| Thrombosis | 0 | 0 | 2 (2) | 2 (2) | 0 | 0 | 2 (1) | 2 (1) | 1 (2) | 0 |
| SSS thrombosis | 0 | 0 | 1 (1) | 1 (1) | 0 | 0 | 1 (1) | 1 (1) | 0 | 0 |
| Pulmonary embolism | 0 | 0 | 2 (2) | 2 (2) | 0 | 0 | 2 (1) | 2 (1) | 0 | 0 |
| Jugular vein thrombosis | 0 | 0 | 1 (1) | 0 | 0 | 0 | 1 (1) | 0 | 0 | 0 |
| Deep vein thrombosis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 (2) | 0 |
| Increased ALT | 2 (6) | 2 (6) | 14 (17) | 8 (10) | 8 (16) | 3 (6) | 24 (14) | 13 (8) | 11 (18) | 7 (11) |
| Increased AST | 2 (6) | 0 | 12 (14) | 4 (5) | 4 (8) | 0 | 18 (11) | 4 (2) | 6 (10) | 3 (5) |
| Increased blood bilirubin‖ | 0 | 0 | 8 (10) | 1 (1) | 3 (6) | 2 (4) | 11 (7) | 3 (2) | 3 (5) | 1 (2) |
| Hyperammonemia | 0 | 0 | 3 (4) | 2 (2) | 0 | 0 | 3 (2) | 2 (1) | 2 (3) | 1 (2) |
| Other commonly reported nonhematologic TRAEs | ||||||||||
| Nausea | 7 (21) | 1 (3) | 20 (24) | 6 (7) | 13 (25) | 2 (4) | 40 (24) | 9 (5) | 27 (44) | 7 (11) |
| Vomiting | 7 (21) | 0 | 22 (27) | 3 (4) | 10 (20) | 1 (2) | 39 (23) | 4 (2) | 36 (59) | 8 (13) |
| Decreased appetite | 3 (9) | 1 (3) | 12 (14) | 3 (4) | 9 (18) | 1 (2) | 24 (14) | 5 (3) | 5 (8) | 0 |
| Fatigue | 3 (9) | 1 (3) | 17 (20) | 0 | 3 (6) | 0 | 23 (14) | 1 (1) | 8 (13) | 0 |
| Febrile neutropenia | 2 (6) | 2 (6) | 11 (13) | 11 (13) | 4 (8) | 4 (8) | 17 (10) | 17 (10) | 3 (5) | 3 (5) |
| Abdominal pain | 2 (6) | 0 | 9 (11) | 2 (2) | 6 (12) | 0 | 17 (10) | 2 (1) | 3 (5) | 1 (2) |
| Hyperglycemia | 3 (9) | 1 (3) | 5 (6) | 2 (2) | 7 (14) | 3 (6) | 15 (9) | 6 (4) | 7 (11) | 6 (10) |
TRAEs were reported as MedDRA (version 22.1) preferred terms. The severity of TRAEs was recorded using CTCAE 5.0. AEs were considered related to JZP458 if the event followed a reasonable temporal sequence from administration and fulfilled ≥1 instance of clinical evidence: the event followed a known or suspected response pattern to the study drug; the event disappeared after stopping the study drug; or the event reappeared after the study drug was restarted. Patients could have experienced multiple events listed as individual preferred terms in the table. TRAEs of interest and other commonly reported (≥10% in IM total or IV cohort) nonhematologic TRAEs (safety analysis population).
CTCAE, Common Terminology Criteria for Adverse Events; MedDRA, Medical Dictionary for Regulatory Activities; SSS, superior sagittal sinus.
Some patients had ≥1 TRAE.
Includes the preferred terms hypersensitivity and drug hypersensitivity.
Includes the preferred terms of rash maculo-papular, rash, and rash erythematous.
Includes the preferred terms of pancreatitis and acute pancreatitis.
Includes the preferred terms blood bilirubin increased and conjugated bilirubin increased.