Table 3.
Overall safety summary by study and treatment group
| Phase 1a Single-Dose Study Treatment Groups | Phase 1b Multiple-Dose Study Treatment Groups | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| BTH1677 | Placebo | BTH1677 | Placebo | |||||||||||
| 0.5 mg/kg (1-h infusion) (n = 3) | 1 mg/kg (1-h infusion) (n = 3) | 2 mg/kg (1-h infusion) (n = 4) | 4 mg/kg (1-h infusion) (n = 2) | 4 mg/kg (2-h infusion) (n = 3) | 6 mg/kg (3-h infusion) (n = 3) | All BTH1677 (n = 18) | All BTH1677 Minus 4 mg/kg 1-h Infusion Groupa (n = 16) | All Placebob (n = 6) | 1 mg/kg (1-h infusion) (n = 3) | 2 mg/kg (1-h infusion) (n = 3) | 4 mg/kg (2-h infusion) (n = 3) | All BTH1677 (n = 9) | All Placebob (n = 3) | |
| Subjects with AEs, n (%)c | 3 (100.0) | 1 (33.3) | 2 (50.0) | 2 (100.0) | 1 (33.3) | 3 (100.0) | 12 (66.7) | 10 (62.5) | 3 (50.0) | 1 (33.3) | 2 (66.7) | 3 (100.0) | 6 (66.7) | 2 (66.7) |
| Mild | 3 (100.0) | 1 (33.3) | 0 (0.0) | 0 (0.0) | 1 (33.3) | 2 (66.7) | 7 (38.9) | 7 (43.8) | 1 (16.7) | 1 (33.3) | 0 (0.0) | 1 (33.3) | 2 (22.2) | 0 (0.0) |
| Moderate | 0 (0.0) | 0 (0.0) | 2 (50.0) | 2 (100.0) | 0 (0.0) | 1 (33.3) | 5 (27.8) | 3 (18.8) | 2 (33.3) | 0 (0.0) | 2 (66.7) | 2 (66.7) | 4 (44.4) | 2 (66.7) |
| Severe | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| AEs, n | 4 | 1 | 3 | 10 | 2 | 8 | 28 | 18 | 10e | 3 | 2 | 3 | 8 | 3 |
| Mean AEs per subject | 1.3 | 1.0 | 1.5 | 5.0 | 2.0 | 2.7 | 2.3 | 1.1 | 3.3e | 3.0 | 1.0 | 1.0 | 1.3 | 1.5 |
| SAEs, n (%) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Deaths, n (%) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Subjects who discontinued due to AEs, n (%) | 0 (0.0) | 0 (0.0) | 1 (25.0) | 2 (100.0) | 0 (0.0) | 1 (33.3) | 4 (22.2) | 2 (12.5) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (33.3) | 1 (11.1) | 1 (33.3) |
| Subjects with AEs assessed as treatment related, n (%)c , d | 2 (66.7) | 1 (33.3) | 1 (25.0) | 2 (100.0) | 0 (0.0) | 3 (100.0) | 9 (50.0) | 7 (43.8) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 2 (66.7) | 2 (22.2) | 1 (33.3) |
| Mild | 2 (66.7) | 1 (33.3) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 2 (66.7) | 5 (27.8) | 5 (31.3) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (33.3) | 1 (11.1) | 0 (0.0) |
| Moderate | 0 (0.0) | 0 (0.0) | 1 (25.0) | 2 (100.0) | 0 (0.0) | 1 (33.3) | 4 (22.2) | 2 (12.5) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (33.3) | 1 (11.1) | 1 (33.3) |
| Severe | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| AEs assessed as treatment related, n | 2 | 1 | 1 | 9 | 0 | 8 | 21 | 12 | 0 | 0 | 0 | 2 | 2 | 1 |
| Mean treatment-related AEs per subject | 1.0 | 1.0 | 1.0 | 4.5 | 0.0 | 2.7 | 2.3 | 1.7 | 0.0 | 0.0 | 0.0 | 1.0 | 1.0 | 1.0 |
AE adverse events
aDuring the Phase 1a study, infusion rate was shown to have an effect on infusion-related AEs which became evident at the 4-mg/kg dose. This resulted in extending infusion time from 1 h to 2 h for a second 4-mg/kg cohort and to 3 h for the 6-mg/kg cohort. This subgroup analysis eliminates the 4-mg/kg 1-h infusion subjects shown to have AEs due to the infusion rate.
bFor subjects receiving placebo, infusion time matched that of the corresponding treatment group.
cA single subject may have multiple AEs with different intensities; only the most severe intensity is included in this count.
dRelatedness definitions differed between the studies; Phase 1a used not related, related, and unknown and Phase 1b used unrelated, unlikely related, possibly related, probably related, definitely related, and unknown. Treatment-related AEs include AEs assessed by the investigator as related for Phase 1a and possibly, probably, or definitely related for Phase1b.
eA single subject in this group reported 8 adverse events.