Table 3.
Treatment-emergent adverse events
|
300 mg (n=49) |
400 mg (n=49) |
|||||
|---|---|---|---|---|---|---|
| Grade 1–2 | Grade 3 | Grade 4 | Grade 1–2 | Grade 3 | Grade 4 | |
| Anaemia | 16 (33%) | 14 (29%) | 1 (2%) | 19 (39%) | 18 (37%) | 0 |
| Fatigue | 19 (39%) | 3 (6%) | 0 | 27 (55%) | 4 (8%) | 0 |
| Back pain | 13 (27%) | 4 (8%) | 0 | 11 (22%) | 3 (6%) | 0 |
| Nausea | 17 (35%) | 1 (2%) | 0 | 13 (27%) | 0 | 0 |
| Platelet count decreased | 9 (18%) | 2 (4%) | 1 (2%) | 12 (24%) | 3 (6%) | 0 |
| Decreased appetite | 13 (27%) | 2 (4%) | 0 | 10 (20%) | 0 | 0 |
| Vomiting | 10 (20%) | 0 | 0 | 15 (31%) | 0 | 0 |
| Weight decreased | 9 (18%) | 1 (2%) | 0 | 15 (31%) | 0 | 0 |
| Diarrhoea | 8 (16%) | 1 (2%) | 0 | 10 (20%) | 1 (2%) | 0 |
| Arthralgia | 8 (16%) | 1 (2%) | 0 | 5 (10%) | 4 (8%) | 0 |
| Hypertension | 9 (18%) | 1 (2%) | 0 | 4 (8%) | 4 (8%) | 0 |
| Neutrophil count decreased | 9 (18%) | 2 (4%) | 0 | 4 (8%) | 2 (4%) | 1 (2%) |
| Dyspnoea | 5 (10%) | 1 (2%) | 0 | 10 (20%) | 1 (2%) | 0 |
| Abdominal pain | 4 (8%) | 0 | 0 | 6 (12%) | 5 (10%) | 1 (2%) |
| Blood creatinine increased | 9 (18%) | 0 | 0 | 6 (12%) | 0 | 0 |
| Oedema peripheral | 6 (12%) | 0 | 0 | 8 (16%) | 1 (2%) | 0 |
| Urinary tract infection | 3 (6%) | 3 (6%) | 0 | 6 (12%) | 3 (6%) | 0 |
| Constipation | 7 (14%) | 0 | 0 | 7 (14%) | 0 | 0 |
| Cough | 3 (6%) | 0 | 0 | 9 (18%) | 0 | 0 |
| Musculoskeletal chest pain | 3 (6%) | 0 | 0 | 9 (18%) | 0 | 0 |
| Musculoskeletal pain | 5 (10%) | 1 (2%) | 0 | 5 (10%) | 1 (2%) | 0 |
| Hypokalaemia | 3 (6%) | 0 | 0 | 8 (16%) | 0 | 0 |
| Muscular weakness | 4 (8%) | 0 | 0 | 5 (10%) | 2 (4%) | 0 |
| White blood cell count decreased | 4 (8%) | 0 | 0 | 6 (12%) | 1 (2%) | 0 |
| Aspartate aminotransferase increased | 3 (6%) | 0 | 1 (2%) | 4 (8%) | 1 (2%) | 0 |
| Alkaline phosphatase increased | 3 (6%) | 0 | 0 | 5 (10%) | 1 (2%) | 0 |
| Dysgeusia | 6 (12%) | 0 | 0 | 3 (6%) | 0 | 0 |
| Haematuria | 5 (10%) | 0 | 0 | 2 (4%) | 2 (4%) | 0 |
| Influenza like illness | 3 (6%) | 0 | 0 | 6 (12%) | 0 | 0 |
| Muscle spasms | 3 (6%) | 0 | 0 | 6 (12%) | 0 | 0 |
| Gamma-glutamyl transferase increased | 3 (6%) | 0 | 0 | 2 (4%) | 2 (4%) | 1 (2%) |
| Lower respiratory tract infection | 4 (8%) | 1 (2%) | 0 | 2 (4%) | 1 (2%) | 0 |
| Lymphocyte count decreased | 2 (4%) | 1 (2%) | 0 | 3 (6%) | 2 (4%) | 0 |
| Pyrexia | 4 (8%) | 2 (4%) | 0 | 2 (4%) | 0 | 0 |
| Alanine aminotransferase increased | 2 (4%) | 0 | 0 | 3 (6%) | 2 (4%) | 0 |
| Groin pain | 3 (6%) | 0 | 0 | 2 (4%) | 2 (4%) | 0 |
| Dizziness | 2 (4%) | 1 (2%) | 0 | 2 (4%) | 1 (2%) | 0 |
| Spinal cord compression | 0 | 1 (2%) | 0 | 0 | 5 (10%) | 0 |
| Blood bilirubin increased | 1 (2%) | 0 | 0 | 3 (6%) | 0 | 1 (2%) |
| Cellulitis | 2 (4%) | 0 | 0 | 2 (4%) | 1 (2%) | 0 |
| Pain | 1 (2%) | 1 (2%) | 0 | 2 (4%) | 1 (2%) | 0 |
| Hydronephrosis | 1 (2%) | 2 (4%) | 0 | 0 | 1 (2%) | 0 |
| Hyponatraemia | 0 | 1 (2%) | 0 | 2 (4%) | 1 (2%) | 0 |
| Myocardial infarction* | 0 | 1 (2%) | 1 (2%) | 0 | 1 (2%) | 0 |
| Acute kidney injury | 1 (2%) | 0 | 1 (2%) | 1 (2%) | 0 | 0 |
| Hyperkalaemia | 0 | 1 (2%) | 0 | 2 (4%) | 0 | 0 |
| Rectal haemorrhage | 0 | 1 (2%) | 0 | 1 (2%) | 1 (2%) | 0 |
| Amylase increased | 0 | 0 | 0 | 1 (2%) | 1 (2%) | 0 |
| Atrial fibrillation | 0 | 0 | 0 | 1 (2%) | 1 (2%) | 0 |
| Circulatory collapse | 0 | 2 (4%) | 0 | 0 | 0 | 0 |
| Confusional state | 1 (2%) | 1 (2%) | 0 | 0 | 0 | 0 |
| Femoral neck fracture | 0 | 1 (2%) | 0 | 1 (2%) | 0 | 0 |
| Femur fracture | 0 | 0 | 0 | 0 | 2 (4%) | 0 |
| Mobility decreased | 1 (2%) | 0 | 0 | 0 | 1 (2%) | 0 |
| Pneumonia | 0 | 0 | 0 | 0 | 2 (4%) | 0 |
| Presyncope | 1 (2%) | 0 | 0 | 0 | 1 (2%) | 0 |
| Pulmonary embolism | 0 | 1 (2%) | 0 | 0 | 1 (2%) | 0 |
| Respiratory tract infection | 1 (2%) | 1 (2%) | 0 | 0 | 0 | 0 |
| Abdominal infection | 0 | 1 (2%) | 0 | 0 | 0 | 0 |
| Acute myeloid leukaemia | 0 | 0 | 1 (2%) | 0 | 0 | 0 |
| Arthritis bacterial | 0 | 1 (2%) | 0 | 0 | 0 | 0 |
| Bronchitis | 0 | 1 (2%) | 0 | 0 | 0 | 0 |
| Cauda equina syndrome | 0 | 0 | 0 | 0 | 1 (2%) | 0 |
| Embolism | 0 | 0 | 0 | 0 | 1 (2%) | 0 |
| Enterocolitis infectious | 0 | 0 | 0 | 0 | 1 (2%) | 0 |
| Febrile neutropenia | 0 | 0 | 0 | 0 | 1 (2%) | 0 |
| Hip fracture | 0 | 1 (2%) | 0 | 0 | 0 | 0 |
| Intestinal obstruction | 0 | 0 | 0 | 0 | 1 (2%) | 0 |
| Jaundice | 0 | 0 | 0 | 0 | 1 (2%) | 0 |
| Neutropenic sepsis | 0 | 0 | 0 | 0 | 1 (2%) | 0 |
| Pyelonephritis | 0 | 0 | 0 | 0 | 1 (2%) | 0 |
| Radiculopathy | 0 | 0 | 0 | 0 | 1 (2%) | 0 |
| Renal colic | 0 | 1 (2%) | 0 | 0 | 0 | 0 |
| Sepsis | 0 | 0 | 0 | 0 | 0 | 1 (2%) |
| Ureteric obstruction | 0 | 1 (2%) | 0 | 0 | 0 | 0 |
| Urosepsis | 0 | 1 (2%) | 0 | 0 | 0 | 0 |
| Vascular pseudoaneurysm | 0 | 0 | 1 (2%) | 0 | 0 | 0 |
| Vision blurred | 0 | 1 (2%) | 0 | 0 | 0 | 0 |
Adverse events were graded according to Common Terminology Criteria for Adverse Events version 4.02, and coded according to the the Medical Dictionary for Regulatory Activities version 22.0. Any grade 1–2 event occurring in 10% or more of patients is reported. All grade 3 and 4 events are reported.
*
One death due to myocardial infarction (grade 5 event deemed a suspected unexpected serious adverse reaction) was reported (not included in table).