3. Common AEs (all grades, >10%; and 3−4 grade) assessed by investigator as related to treatment by dose.
| AEs | 10−80 mg/d (n=16) | 120 mg/d (n=16) | 160 mg/d (n=16) | 200 mg/d (n=13) | 300 mg/d (n=14) | 400 mg/d (n=4) | Total (N=79) | |||||||||||||
| All
grades |
3−4 grade | All
grades |
3−4 grade | All
grades |
3−4 grade | All
grades |
3−4 grade | All
grades |
3−4 grade | All
grades |
3−4 grade | All
grades |
3−4 grade | |||||||
| AE, adverse event; WBC, white blood cell; ALT, alanine aminotransferase; AST, aspartate aminotransferase; RBC, red blood cell. | ||||||||||||||||||||
| Anemia | 5 (31.3) | 1 (6.3) | 8 (50.0) | 2 (12.5) | 9 (56.3) | 1 (6.3) | 8 (61.5) | 1 (7.7) | 8 (57.1) | 0 | 4 (100) | 1 (25.0) | 42 (53.2) | 6 (7.6) | ||||||
| WBC count decreased | 7 (43.8) | 0 | 7 (43.8) | 3 (18.8) | 4 (25.0) | 0 | 5 (38.5) | 0 | 4 (28.6) | 0 | 3 (75.0) | 0 | 30 (38.0) | 3 (3.8) | ||||||
| Neutrophil count decreased | 4 (25.0) | 0 | 6 (37.5) | 3 (18.8) | 1 (6.3) | 0 | 5 (38.5) | 0 | 1 (7.1) | 0 | 2 (50.0) | 1 (25.0) | 19 (24.1) | 4 (5.1) | ||||||
| Platelet count decreased | 2 (12.5) | 0 | 2 (12.5) | 1 (6.3) | 3 (18.8) | 0 | 2 (15.4) | 1 (7.7) | 2 (14.3) | 0 | 3 (75.0) | 1 (25.0) | 14 (17.7) | 3 (3.8) | ||||||
| ALT increased | 3 (18.8) | 0 | 1 (6.3) | 0 | 4 (25.0) | 0 | 2 (15.4) | 0 | 2 (14.3) | 0 | 2 (50.0) | 0 | 14 (17.7) | 0 | ||||||
| AST increased | 2 (12.5) | 0 | 2 (12.5) | 0 | 4 (25.0) | 0 | 4 (30.8) | 0 | 2 (14.3) | 0 | 1 (25.0) | 0 | 15 (19.0) | 0 | ||||||
| Blood albumin decreased | 1 (6.3) | 0 | 3 (18.8) | 0 | 4 (25.0) | 0 | 4 (30.8) | 0 | 3 (21.4) | 0 | 1 (25.0) | 0 | 16 (20.3) | 0 | ||||||
| Blood triglycerides increased | 2 (12.5) | 0 | 11 (68.8) | 0 | 1 (6.3) | 0 | 4 (30.8) | 0 | 5 (35.7) | 0 | 0 | 0 | 23 (29.1) | 0 | ||||||
| Blood cholesterol increased | 2 (12.5) | 0 | 5 (31.3) | 0 | 1 (6.3) | 0 | 2 (15.4) | 0 | 4 (28.6) | 0 | 0 | 0 | 14 (17.7) | 0 | ||||||
| Blood potassium decreased | 1 (6.3) | 0 | 3 (18.8) | 0 | 4 (25.0) | 1 (6.3) | 0 | 0 | 0 | 0 | 0 | 0 | 8 (10.1) | 1 (1.3) | ||||||
| Blood calcium decreased | 2 (12.5) | 0 | 5 (31.3) | 0 | 4 (25.0) | 1 (6.3) | 1 (7.7) | 0 | 0 | 0 | 0 | 0 | 12 (15.2) | 1 (1.3) | ||||||
| Blood creatinine increased | 0 | 0 | 1 (6.3) | 0 | 1 (6.3) | 0 | 2 (15.4) | 0 | 4 (28.6) | 0 | 0 | 0 | 8 (10.1) | 0 | ||||||
| Lipase increased | 3 (18.8) | 1 (6.3) | 3 (18.8) | 0 | 3 (18.8) | 1 (6.3) | 1 (7.7) | 0 | 0 | 0 | 1 (25.0) | 1 (25.0) | 11 (13.9) | 3 (3.8) | ||||||
| Amylase increased | 0 | 0 | 2 (12.5) | 0 | 3 (18.8) | 0 | 1 (7.7) | 0 | 1 (7.1) | 0 | 1 (25.0) | 0 | 8 (10.1) | 0 | ||||||
| Proteinuria | 6 (37.5) | 1 (6.3) | 3 (18.8) | 0 | 4 (25.0) | 0 | 1 (7.7) | 0 | 1 (7.1) | 0 | 0 | 0 | 15 (19.0) | 1 (1.3) | ||||||
| WBC urine positive | 2 (12.5) | 0 | 2 (12.5) | 0 | 2 (12.5) | 0 | 1 (7.7) | 0 | 1 (7.1) | 0 | 0 | 0 | 8 (10.1) | 0 | ||||||
| RBC urine positive | 0 | 0 | 3 (18.8) | 0 | 1 (6.3) | 0 | 1 (7.7) | 0 | 3 (21.4) | 0 | 0 | 0 | 8 (10.1) | 0 | ||||||
| Nausea | 6 (37.5) | 0 | 4 (25.0) | 1 (6.3) | 7 (43.8) | 0 | 2 (15.4) | 0 | 6 (42.9) | 0 | 2 (50.0) | 1 (25.0) | 27 (34.2) | 2 (2.5) | ||||||
| Vomiting | 2 (12.5) | 0 | 2 (12.5) | 0 | 3 (18.8) | 0 | 2 (15.4) | 0 | 4 (28.6) | 1 (7.1) | 1 (25.0) | 1 (25.0) | 14 (17.7) | 2 (2.5) | ||||||
| Decreased appetite | 2 (12.5) | 0 | 5 (31.3) | 2 (12.5) | 8 (50.0) | 0 | 3 (23.1) | 0 | 3 (21.4) | 0 | 2 (50.0) | 0 | 23 (29.1) | 2 (2.5) | ||||||
| Diarrhea | 0 | 0 | 2 (12.5) | 0 | 3 (18.8) | 0 | 6 (46.2) | 1 (7.7) | 3 (21.4) | 1 (7.1) | 0 | 0 | 14 (17.7) | 2 (2.5) | ||||||
| Constipation | 0 | 0 | 2 (12.5) | 0 | 2 (12.5) | 0 | 3 (23.1) | 0 | 1 (7.1) | 0 | 0 | 0 | 8 (10.1) | 0 | ||||||
| Abdominal pain | 1 (6.3) | 0 | 3 (18.8) | 0 | 3 (18.8) | 1 (6.3) | 3 (23.1) | 0 | 6 (42.9) | 0 | 2 (50.0) | 2 (50.0) | 18 (22.8) | 3 (3.8) | ||||||
| Abdominal distension | 1 (6.3) | 1 (6.3) | 2 (12.5) | 0 | 5 (31.3) | 0 | 2 (15.4) | 0 | 3 (21.4) | 0 | 0 | 0 | 13 (16.5) | 1 (1.3) | ||||||
| Back pain | 1 (6.3) | 0 | 1 (6.3) | 0 | 3 (18.8) | 0 | 1 (7.7) | 0 | 3 (21.4) | 0 | 1 (25.0) | 0 | 10 (12.7) | 0 | ||||||
| Fatigue | 4 (25.0) | 0 | 7 (43.8) | 0 | 11 (68.8) | 2 (12.5) | 7 (53.8) | 1 (7.7) | 6 (42.9) | 0 | 3 (75.0) | 1 (25.0) | 38 (48.1) | 3 (3.8) | ||||||
| Weight decreased | 0 | 0 | 1 (6.3) | 0 | 3 (18.8) | 0 | 2 (15.4) | 0 | 0 | 0 | 2 (50.0) | 0 | 8 (10.1) | 0 | ||||||