Table 4.

Most frequent treatment emergent adverse events (reported by >5% of patients) and serious adverse events (reported by >2% of patients)

System Organ Class and Adverse Event/Serious Adverse Eventn (%)
Most frequent treatment emergent adverse events (reported by >5% of patients)
 Gastrointestinal disorders
  Nausea14 (9.7)
  Diarrhea12 (8.3)
  Constipation9 (6.2)
  Vomiting8 (5.5)
 General disorders and administrative site conditions
  Peripheral edema18 (12.4)
 Infections and infestations
  Urinary tract infection14 (9.7)
  Nasopharyngitis13 (9.0)
  Sinusitis8 (5.5)
 Nervous system disorders
  Dizziness9 (6.2)
  Headache8 (5.5)
 Vascular disorders
  Hypertension11 (7.6)
Most frequent serious adverse eventsa (reported by >2% of patients)
 Cardiac disorders
  Cardiac failure, congestive5 (3.4)
 Gastrointestinal disorders
  Pancreatitis3 (2.1)
 Infections and infestations
  Cellulitis3 (2.1)
 Metabolism and nutrition disorders
  Hyponatremia3 (2.1)
 Renal and urinary disordersb
  Renal failure, acute4 (2.8)
  Renal failure, chronic3 (2.1)
  • a Regarding serious cardiovascular events, all patients had been in the study for <10 weeks, and none had achieved target hemoglobin of 11 g/dl before the onset of the serious adverse event. During their treatment period, patients had hemoglobin <10 g/dl for 18% of the exposure time. Six of nine (67%) of serious cardiovascular events occurred when hemoglobin <10 g/dl. The remainder of the serious cardiovascular events were experienced while patient hemoglobin was 10–11 g/dl. No serious cardiovascular events were reported when hemoglobin was ≥11 g/dl during the study, although this hemoglobin range accounted for 52% of total patient exposure.

  • b Renal serious adverse events and dialysis initiation. Of four patients who reported acute renal serious adverse event, three fully recovered from the events, and one progressed to dialysis. The three patients reporting chronic renal serious adverse event initiated dialysis. Clinical scenarios consistent with volume depletion were judged to be a major contributing factor in a majority of the renal serious adverse events. Another patient initiated hemodialysis without reporting a serious adverse event. Of the five patients who initiated dialysis during the study, two had stage 5 CKD with eGFR<15 ml/min per 1.73 m2 at baseline, and the other three patients had borderline stage 4/5 CKD with baseline eGFR values of 15 or 16 ml/min per 1.73 m2.