Table 2.

Overview of adverse events during tolvaptan treatment

Subjects and Adverse EventsPrior Trial ParticipationTotal, n=1800, n (%)a
From Replicating Evidence of Preserved Renal Function: An Investigation of Tolvaptan Safety and Efficacy in Autosomal Dominant Polycystic Kidney Disease Tolvaptan, n=505, n (%)From Replicating Evidence of Preserved Renal Function: An Investigation of Tolvaptan Safety and Efficacy in Autosomal Dominant Polycystic Kidney Disease Placebo, n=569, n (%)From Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes 4:4 Tolvaptan, n=717, n (%)
Subjects with AEs473 (94)531 (93)643 (90)1656 (92)
AEs35674313396311,932
Subjects with treatment-emergent AEs473 (94)531 (93)640 (89)1653 (92)
Treatment-emergent AEs29653678329710,019
Subjects with serious treatment-emergent AEsb87 (17)96 (17)103 (14)289 (16)
Subjects with severe treatment-emergent AEsc74 (15)78 (14)83 (12)238 (13)
Subjects with treatment-emergent AEs both serious and severe43 (9)40 (7)44 (6)128 (7)
Subjects discontinued trial drug due to AEs33 (7)65 (11)38 (5)137 (8)
Deathsd1 (0.2)5 (0.9)3 (0.4)9 (0.5)
  • AE, adverse event.

  • a The table has no column for subjects who entered the extension directly from the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes (TEMPO) 3:4 or NOCTURNE trial due to the small number of subjects (n=9; four from TEMPO 3:4 tolvaptan, two from NOCTURNE tolvaptan, and three from TEMPO 3:4 placebo) from those trials. Data from these subjects are included in the total column.

  • b Serious AEs were defined as those that resulted in any of the following outcomes: death; life-threatening risk in the opinion of the investigator; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; requires inpatient hospitalization or prolongs hospitalization; congenital anomaly/birth defect; or other medically significant events that, on the basis of appropriate medical judgment, may jeopardize the subject and may require medical or surgical intervention.

  • c AEs were graded as severe in cases resulting in an inability to work or perform normal daily activity.

  • d Causes were tuberculosis in a subject from the Replicating Evidence of Preserved Renal Function: An Investigation of Tolvaptan Safety and Efficacy in Autosomal Dominant Polycystic Kidney Disease (REPRISE) tolvaptan trial; aortic dissection/cardiogenic shock, CKD/septic shock, meningeal metastases, acute respiratory distress syndrome, and sudden death in subjects from REPRISE placebo; and cardiac arrest, subarachnoid hemorrhage, and ruptured cerebral aneurysm in subjects from TEMPO 4:4.