Canakinumab pooled dose | Placebo | ||||
---|---|---|---|---|---|
Low dose | Intermediate dose | Medium dose | High dose | ||
I. Haematology parameters | |||||
WBC (total) (109/L), N | 20 | 245 | 262 | 136 | 342 |
Any grade 1–4 abnormality, n | 0 | 19 | 18 | 10 | 14 |
IR (%) | 0.0 | 2.14 | 3.22 | 1.86 | 1.25 |
Dose trend test, P value | 0.0884 | ||||
G1 (<LLN–3.0), n (%) | 0 | 18 (7.3) | 15 (5.7) | 10 (7.4) | 13 (3.8) |
IR (%) | 0.0 | 2.03 | 2.68 | 1.86 | 1.16 |
G2 (<3.0–2.0), n (%) | 0 | 1 (0.4) | 4 (1.5) | 1 (0.7) | 1 (0.3) |
IR (%) | 0.0 | 0.11 | 0.68 | 0.18 | 0.09 |
Absolute neutrophil counts (Seg. + bands) (109/L), N | 20 | 222 | 258 | 93 | 288 |
Any grade 1–4 abnormality, n | 1 | 21 | 27 | 13 | 10 |
IR (%) | 0.89 | 2.68 | 4.95 | 4.61 | 1.22 |
Dose trend test, P value | 0.0001 | ||||
G1 (<LLN–1.5), n (%) | 0 | 17 (7.7) | 23 (8.9) | 13 (14.0) | 7 (2.4) |
IR (%) | 0.0 | 2.13 | 4.17 | 4.59 | 0.85 |
G2 (<1.5–1.0), n (%) | 1 (5.0) | 6 (2.7) | 7 (2.7) | 2 (2.2) | 2 (0.7) |
IR (%) | 0.89 | 0.74 | 1.26 | 0.66 | 0.24 |
Platelet counts (direct) (109/L), N | 20 | 245 | 260 | 136 | 342 |
Any grade 1–4 abnormality, n | 1 | 11 | 9 | 4 | 11 |
IR (%) | 0.92 | 1.23 | 1.57 | 0.73 | 1.00 |
Dose trend test, P value | 0.9488 | ||||
G1 (<LLN–75), n (%) | 1 (5.0) | 10 (4.1) | 9 (3.5) | 4 (2.9) | 11 (3.2) |
IR (%) | 0.92 | 1.11 | 1.57 | 0.73 | 1.00 |
G2 (<75–50), n (%) | 0 | 0 | 0 | 1 (0.7) | 0 |
IR (%) | 0.0 | 0.0 | 0.0 | 0.18 | 0.0 |
Absolute lymphocyte counts (109/L), N | 20 | 222 | 258 | 93 | 288 |
Any grade 1–4 abnormality, n | 0 | 2 | 3 | 1 | 7 |
IR (%) | 0.0 | 0.25 | 0.53 | 0.33 | 0.85 |
Dose trend test, P value | 0.2241 | ||||
G1 (<LLN–0.8), n (%) | 0 | 0 | 1 (0.4) | 0 | 3 (1.0) |
IR (%) | 0.0 | 0.0 | 0.18 | 0.0 | 0.36 |
G2 (<0.8–0.5), n (%) | 0 | 2 (0.9) | 2 (0.8) | 1 (1.1) | 4 (1.4) |
IR (%) | 0.0 | 0.25 | 0.36 | 0.33 | 0.48 |
Haemoglobin (g/L), N | 20 | 245 | 262 | 136 | 342 |
Any grade 1–4 abnormality, n | 8 | 49 | 36 | 31 | 76 |
IR (%) | 9.20 | 6.27 | 6.83 | 6.68 | 7.97 |
Dose trend test, P value | 0.1239 | ||||
G1 (<LLN–100), n (%) | 8 (40.0) | 49 (20.0) | 33 (12.6) | 30 (22.1) | 73 (21.3) |
IR (%) | 9.09 | 6.23 | 6.24 | 6.41 | 7.63 |
G2 (<100–80), n (%) | 1 (5.0) | 5 (2.0) | 3 (1.1) | 2 (1.5) | 5 (1.5) |
IR (%) | 0.90 | 0.54 | 0.51 | 0.36 | 0.44 |
II. Biochemistry parameters | |||||
SGPT (ALT) (U/L), N | 20 | 245 | 262 | 136 | 343 |
Any grade 1–4 abnormality, n | 0 | 2 | 4 | 5 | 2 |
IR (%) | 0.0 | 0.21 | 0.69 | 0.88 | 0.17 |
Dose trend test, P value | 0.0158 | ||||
G1 (>3–5×ULN), n (%) | 0 | 2 (0.8) | 4 (1.5) | 5 (3.7) | 2 (0.6) |
IR (%) | 0.0 | 0.21 | 0.69 | 0.88 | 0.17 |
SGOT (AST) (U/L), N | 20 | 245 | 256 | 136 | 342 |
Any grade 1–4 abnormality, n | 0 | 1 | 0 | 2 | 0 |
IR (%) | 0.0 | 0.11 | 0.0 | 0.35 | 0.0 |
Dose trend test, P value | 0.0777 | ||||
G1 (>3–5×ULN), n (%) | 0 | 1 (0.4) | 0 | 2 (1.5) | 0 |
IR (%) | 0.0 | 0.11 | 0.0 | 0.35 | 0.0 |
Bilirubin (total) (μmol/L), N | 20 | 245 | 265 | 136 | 344 |
Any grade 1–4 abnormality, n | 0 | 0 | 3 | 4 | 6 |
IR (%) | 0.0 | 0.0 | 0.52 | 0.70 | 0.52 |
Dose trend test, P value | 0.6430 | ||||
G1 (>1.5–2×ULN), n (%) | 0 | 0 | 2 (0.8) | 3 (2.2) | 5 (1.5) |
IR (%) | 0.0 | 0.0 | 0.34 | 0.52 | 0.44 |
G2 (>2–3×ULN), n (%) | 0 | 0 | 2 (0.8) | 2 (1.5) | 0 |
IR (%) | 0.0 | 0.0 | 0.34 | 0.35 | 0.0 |
Alkaline phosphatase, serum (U/L), N | 20 | 245 | 263 | 136 | 344 |
Any grade 1–4 abnormality, n | 0 | 0 | 0 | 0 | 1 |
IR (%) | 0.0 | 0.0 | 0.0 | 0.0 | 0.09 |
Dose trend test, P value | 0.2357 | ||||
G1 (>2–3×ULN), n (%) | 0 | 0 | 0 | 0 | 1 (0.3) |
IR (%) | 0.0 | 0.0 | 0.0 | 0.0 | 0.09 |
G2 (>3–5×ULN), n (%) | 0 | 0 | 0 | 0 | 1 (0.3) |
IR (%) | 0.0 | 0.0 | 0.0 | 0.0 | 0.09 |
Creatinine (umol/L), N | 20 | 245 | 265 | 136 | 344 |
Any grade 1–4 abnormality, n | 1 | 10 | 11 | 6 | 10 |
IR (%) | 0.91 | 1.06 | 1.89 | 1.06 | 0.88 |
Dose trend test, P value | 0.3490 | ||||
G1 (>ULN–1.5×ULN), n (%) | 1 (5.0) | 10 (4.1) | 11 (4.2) | 6 (4.4) | 10 (2.9) |
IR (%) | 0.91 | 1.06 | 1.88 | 1.06 | 0.88 |
G2 (>1.5–3×ULN), n (%) | 0 | 1 (0.4) | 1 (0.4) | 0 | 0 |
IR (%) | 0.0 | 0.11 | 0.17 | 0.0 | 0.0 |