Table 1.
Summary of patient characteristics.
| Characteristic | DOSE LEVEL | Total (n=71) | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
|
| ||||||||||
| 50/50 mg (n = 9) | 100/50 mg (n = 6) | 100/100 mg (n = 5) | 150/100 mg (n = 7) | 150/150 mg (n = 6) | 200/200 mg (n = 6) | 300/300 mg (n = 8) | 400/400 mg (n = 16) | 500/500 mg (n = 8) | ||
| Demographics | ||||||||||
| Age, years, mean (range) | 49.2 (28.0 – 64.0) | 51.0 (39.0 – 61.0) | 59.8 (49.0 – 84.0) | 56.1 (47.0 – 64.0) | 50.0 (37.0 – 62.0) | 58.2 (50.0 – 64.0) | 50.9 (33.0 – 66.0) | 56.2 (40.0 – 74.0) | 50.5 (37.0 – 65.0) | 53.5 (28.0 – 84.0) |
| Body weight, kg, mean (range) | 70.4 (45.0 – 98.2) | 81.6 (59.0 – 102) | 75.9 (61.4 – 92.1) | 68.9 (46.3 – 92.0) | 64.2 (51.8 – 84.0) | 87.3 (64.5 – 109) | 90.1 (58.3 – 113) | 73.4 (51.3 – 119) | 66.2 (47.0 – 92.2) | 74.9 (45.0 – 119) |
| Lean body mass, kg, mean (range) | 47.5 (36.9 – 62.6) | 49.2 (39.8 – 53.5) | 47.5 (43.1 – 54.4) | 45.3 (37.3 – 51.2) | 45.3 (42.9 – 48.4) | 52.4 (43.2 – 61.3) | 52.4 (44.2 – 58.3) | 47.4 (36.6 – 63.7) | 42.6 (38.6 – 49.8) | 47.6 (36.6 – 63.7) |
| Height, cm, mean (range) | 167 (160 – 177) | 163 (157 – 175) | 163 (155 – 174) | 163 (155 – 170) | 167 (160 – 172) | 167 (161 – 173) | 165 (160 – 179) | 165 (154 – 175) | 159 (152 – 165) | 164 (152 – 179) |
| Body mass index, kg/m2, mean (range) | 25.2 (17.6 – 31.9) | 30.8 (20.0 – 40.9) | 28.7 (20.3 – 35.8) | 25.8 (18.1 – 35.5) | 23.3 (18.0 – 32.8) | 31.1 (24.8 – 36.4) | 33.3 (20.7 – 44.1) | 26.9 (19.4 – 40.6) | 26.5 (17.8 – 37.2) | 27.8 (17.6 – 44.1) |
| Sex, n (%) | ||||||||||
| Female | 8 (89%) | 6 (100%) | 5 (100%) | 7 (100%) | 6 (100%) | 6 (100%) | 8 (100%) | 15 (94%) | 8 (100%) | 69 (97%) |
| Male | 1 (11%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | 1 (6%) | 0 (0%) | 2 (3%) |
| Clinical | ||||||||||
| Serum Creatinine, mg/dL, mean (range) | 0.77 (0.65–1.15) | 0.85 (0.56–1.00) | 0.80 (0.50–1.32) | 0.85 (0.57–1.10) | 0.69 (0.47–0.90) | 1.00 (0.60–1.37) | 0.79 (0.62–1.37) | 0.71 (0.40–1.30) | 0.73 (0.50–0.80) | 0.78 (0.4–1.37) |
| CLCR, mL/min*, mean (range) | 96.8 (71.3 – 120) | 95.4 (61.8 – 120) | 92.8 (66.7 – 120) | 89.6 (48.5 – 120) | 98.4 (74.5 – 120) | 85.4 (51.6 – 120) | 108 (72.0 – 120) | 95.4 (48.9 – 120) | 90.7 (65.9 – 120) | 95.2 (48.5 – 120) |
| Albumin (g/L), mean (range) | 3.51 (2.00 – 4.30) | 3.95 (3.60 – 4.30) | 3.72 (3.10 – 4.40) | 3.87 (2.60 – 4.50) | 3.80 (3.20 – 4.40) | 3.73 (2.70 – 4.20) | 3.88 (3.20 – 4.40) | 3.67 (2.60 – 4.30) | 3.93 (3.60 – 4.20) | 3.77 (2.00 – 4.50) |
| ALT (U/L), mean (range) | 28.2 (7.00 – 73.0) | 25.5 (8.00 – 55.0) | 17.8 (15.0 – 23.0) | 40.4 (13.0 – 124) | 27.8 (10.0 – 45.0) | 27.5 (14.0 – 42.0) | 20.4 (13.0 – 39.0) | 32.2 (13.0 – 135) | 27.9 (17.0 – 43.0) | 28.3 (7.00 – 135) |
| AST (U/L), mean (range) | 44.4 (21.0 – 117) | 31.3 (18.0 – 49.0) | 28.2 (18.0 – 53.0) | 44.0 (21.0 – 81.0) | 34.8 (20.0 – 55.0) | 29.3 (22.0 – 52.0) | 23.4 (11.0 – 32.0) | 33.0 (13.0 – 76.0) | 32.4 (21.0 – 54.0) | 33.7 (11.0 – 117) |
| Total bilirubin (mg/dL), mean (range) | 0.39 (0.10 – 0.70) | 0.40 (0.30 – 0.70) | 0.56 (0.30 – 0.90) | 0.49 (0.30 – 0.90) | 0.50 (0.30 – 0.90) | 0.67 (0.40 – 0.80) | 0.47 (0.20 – 0.80) | 0.49 (0.20 – 1.00) | 0.64 (0.20 – 1.10) | 0.51 (0.10 – 1.10) |
| ECOG performance Status, n (%) | ||||||||||
| 0 | 4 (44%) | 2 (33%) | 3 (60%) | 4 (57%) | 3 (50%) | 3 (50%) | 5 (63%) | 12 (75%) | 7 (88%) | 43 (61%) |
| 1 | 4 (44%) | 2 (33%) | 1 (20%) | 3 (43%) | 3 (50%) | 3 (50%) | 2 (25%) | 3 (19%) | 1 (13%) | 22 (31%) |
| 2 | 1 (11%) | 2 (33%) | 1 (20%) | 0 (0%) | 0 (0%) | 0 (0%) | 1 (13%) | 1 (6%) | 0 (0%) | 6 (8%) |
Notes: CLCR was estimated using Cockcroft–Gault formula19. Estimated CLCR values higher than 120 were assigned a value of 120 mL/min as a reasonable upper limit for the analysis.
67 of the 71 patients had pharmacokinetic samples for veliparib, and 38 out of the 67 had M8 pharmacokinetic samples collected.
41 of the 71 patients had PAR levels in PBMC collected. 4 patients did not have pharmacokinetic results but had PAR levels in PBMC.
Dose level was depicted as am/pm dose in mg.