Table 3.

TEMPO 3:4: treatment-emergent, statin-related adverse events by system organ class and Medical Dictionary for Regulatory Activities preferred term

SOC/Adverse EventTolvaptan+Statin (n=129) n (%)Placebo+Statin (n=64) n (%)Difference in Proportions % (95% CI)P Value Tolvaptan+Statin versus Placebo+StatinTolvaptan Alone (n=832) n (%)Placebo Alone (n=419) n (%)Difference in Proportions % (95% CI)P Value Tolvaptan Alone versus Placebo AloneP Value for the Interactiona
Gastrointestinal disorders
 Abdominal distension5 (3.9)1 (1.6)2.3 (−3.4 to 8.0)0.6742 (5.0)15 (3.6)1.5 (−1.0 to 4.0)0.250.61
 Abdominal pain12 (9.3)5 (7.8)1.5 (−7.9 to 10.9)1.0050 (6.0)27 (6.4)−0.4 (−3.5 to 2.6)0.800.66
 Constipation11 (8.5)2 (3.1)5.4 (−2.2 to 13.0)0.2370 (8.4)10 (2.4)6.0 (3.5 to 8.6)<0.0010.76
 Diarrhea17 (13.2)5 (7.8)5.4 (−4.6 to 15.3)0.34111 (13.3)48 (11.5)1.9 (−2.1 to 5.9)0.370.47
 Dyspepsia16 (12.4)3 (4.7)7.7 (−1.1 to 16.6)0.1260 (7.2)13 (3.1)4.1 (1.5 to 6.7)0.0030.81
 Flatulence1 (0.8)0 (0.0)0.8 (−1.9 to 3.5)1.007 (0.8)1 (0.2)0.6 (−0.4 to 1.6)0.280.71
 Nausea9 (7.0)7 (10.9)−4.0 (−13.9 to 6.0)0.4189 (10.7)50 (11.9)−1.2 (−5.2 to 2.7)0.510.51
General disorders and administration site conditions
 Asthenia7 (5.4)2 (3.1)2.3 (−4.7 to 9.3)0.7250 (6.0)25 (6.0)0.0 (−2.9 to 3.0)1.000.50
Investigations
 ALT increased10 (7.8)4 (6.3)1.5 (−7.2 to 10.2)1.0029 (3.5)13 (3.1)0.4 (−1.9 to 2.6)0.870.87
 AST increased12 (9.3)3 (4.7)4.6 (−3.8 to 13.0)0.3924 (2.9)13 (3.1)−0.2 (−2.4 to 2.0)0.860.27
 Blood ALP increased0 (0.0)0 (0.0)3 (0.4)1 (0.2)0.1 (−0.7 to 0.9)1.00
 Blood bilirubin increased1 (0.8)0 (0.0)0.8 (−1.9 to 3.5)1.001 (0.1)2 (0.5)−0.4 (−1.2 to 0.5)0.260.25
 Blood CPK increased2 (1.6)0 (0.0)1.6 (−1.8 to 4.9)1.004 (0.5)1 (0.2)0.2 (−0.6 to 1.1)0.670.50
 Blood glucose increased3 (2.3)0 (0.0)2.3 (−1.4 to 6.1)0.554 (0.5)1 (0.2)0.2 (−0.6 to 1.1)0.670.41
Musculoskeletal and connective tissue disorders
 Arthralgia9 (7.0)4 (6.3)0.7 (−7.8 to 9.3)1.0060 (7.2)24 (5.7)1.5 (−1.5 to 4.5)0.340.85
 Back pain17 (13.2)12 (18.8)−5.6 (−17.9 to 6.8)0.39116 (13.9)76 (18.1)−4.2 (−8.8 to 0.4)0.060.81
 Myalgia7 (5.4)5 (7.8)−2.4 (−11.2 to 6.4)0.5443 (5.2)11 (2.6)2.5 (0.2 to 4.9)0.040.11
 Pain in extremity8 (6.2)6 (9.4)−3.2 (−12.6 to 6.3)0.5634 (4.1)21 (5.0)−0.9 (−3.6 to 1.7)0.470.71
Nervous system disorders
 Headache32 (24.8)20 (31.3)−6.4 (−21.2 to 8.3)0.39209 (25.1)101 (24.1)1 (−4.2 to 6.2)0.730.30
  • Myopathy and rhabdomyolysis were not reported by any subject. TEMPO 3:4, Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes 3:4 trial; SOC, system organ class; 95% CI, 95% confidence interval; ALT, alanine transaminase; AST, aspartate transaminase; ALP, alkaline phosphatase; —, numbers not sufficient for analysis; CPK, creatine phosphokinase.

  • a Derived by the Breslow–Day test to evaluate the interaction of statin use with the odds ratio of an adverse event.