Table 3.
Treatment-emergent adverse events under forced upward titration conditions
| 0.5 mL/min/site (N = 16; Inf = 220) | 1 mL/min/site (N = 16; Inf = 208) | 2 mL/min/site (N = 14; Inf = 198) | ||||
|---|---|---|---|---|---|---|
| n (%) | E (rate) | n (%) | E (rate) | n (%) | E (rate) | |
| Any TEAE | 5 (31.3) | 14 (0.064) | 9 (56.3) | 23 (0.111) | 7 (50.0) | 16 (0.081) |
| Treatment-related | 3 (18.8) | 9 (0.041) | 5 (31.3) | 18 (0.087) | 3 (21.4) | 6 (0.030) |
| Intensity of TEAEs | ||||||
|
Mild Moderate Severe |
5 (31.3) 0 0 |
14 (0.064) 0 0 |
8 (50.0) 0 1 (6.3)a |
22 (0.106) 0 1 (0.005)a |
7 (50.0) 3 (21.4) 0 |
13 (0.066) 3 (0.015) 0 |
| Serious TEAEs | 0 | 0 | 1 (6.3)a | 1 (0.005)a | 0 | 0 |
| Treatment-related | 0 | 0 | 0 | 0 | 0 | 0 |
| Deaths | 0 | 0 | 0 | 0 | 0 | 0 |
| Study discontinuation due to TEAE | 0 | 0 | 1 (6.3)a | 1 (0.005)a | 0 | 0 |
| Treatment-related | 0 | 0 | 0 | 0 | 0 | 0 |
| Study drug withdrawal due to TEAE | 0 | 0 | 1 (6.3)a | 1 (0.005)a | 0 | 0 |
| Treatment-related | 0 | 0 | 0 | 0 | 0 | 0 |
| Local TEAEs | 3 (18.8) | 6 (0.027) | 4 (25.0) | 17 (0.082) | 2 (14.3) | 5 (0.025) |
| Treatment-related | 2 (12.5) | 5 (0.023) | 4 (25.0) | 17 (0.082) | 2 (14.3) | 5 (0.025) |
| Most common (> 1 event at any flow rate) TEAEs by preferred term | ||||||
| Injection site pain | 1 (6.3) | 4 (0.018) | 2 (12.5) | 4 (0.019) | 1 (7.1) | 1 (0.005) |
| Injection site bruising | 0 | 0 | 1 (6.3) | 2 (0.010) | 1 (7.1) | 3 (0.015) |
| Injection site swelling | 1 (6.3) | 1 (0.005) | 1 (6.3) | 3 (0.014) | 1 (7.1) | 1 (0.005) |
| Injection site erythema | 0 | 0 | 1 (6.3) | 3 (0.014) | 0 | 0 |
| Injection site discoloration | 0 | 0 | 1 (6.3) | 2 (0.010) | 0 | 0 |
| Injection site pruritus | 0 | 0 | 1 (6.3) | 2 (0.010) | 0 | 0 |
| Diarrhea | 2 (12.5) | 3 (0.014) | 1 (6.3) | 1 (0.005) | 0 | 0 |
| Nausea | 2 (12.5) | 3 (0.014) | 0 | 0 | 0 | 0 |
| Upper respiratory tract infection | 0 | 0 | 0 | 0 | 2 (14.3) | 2 (0.010) |
| Most common (> 1 event at any flow rate) treatment-related TEAEs by preferred term | ||||||
| Injection site pain | 1 (6.3) | 4 (0.018) | 2 (12.5) | 4 (0.019) | 1 (7.1) | 1 (0.005) |
| Injection site bruising | 0 | 0 | 1 (6.3) | 2 (0.010) | 1 (7.1) | 3 (0.015) |
| Injection site swelling | 1 (6.3) | 1 (0.005) | 1 (6.3) | 3 (0.014) | 1 (7.1) | 1 (0.005) |
| Injection site erythema | 0 | 0 | 1 (6.3) | 3 (0.014) | 0 | 0 |
| Injection site discoloration | 0 | 0 | 1 (6.3) | 2 (0.010) | 0 | 0 |
| Injection site pruritus | 0 | 0 | 1 (6.3) | 2 (0.010) | 0 | 0 |
| Diarrhea | 1 (6.3) | 2 (0.009) | 1 (6.3) | 1 (0.005) | 0 | 0 |
| Nausea | 1 (6.3) | 2 (0.009) | 0 | 0 | 0 | 0 |
Rate = number of events/total number of infusions prior to patient’s start date of non-response
Excludes TEAEs occurring after non-response
E, number of events; Inf, infusions; n, number of patients; TEAE, treatment-emergent adverse event
aOne patient with a documented medical history of depression had a severe, unrelated serious TEAE (suicide attempt) that led to study discontinuation after administering 5 of 8 planned infusions at the 1.0-mL/min rate