Table 4.

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

SOC/Adverse EventTolvaptan+Statin (n=203) n (%)Placebo+Statin (n=201) n (%)Difference in Proportions % (95% CI)P Value Tolvaptan+Statin versus Placebo+StatinTolvaptan Alone (n=478) n (%)Placebo Alone (n=484) n (%)Difference in Proportions % (95% CI)P Value Tolvaptan Alone versus Placebo AloneP Value for the Interactiona
Gastrointestinal disorders
 Abdominal distension0 (0.0)3 (1.5)−1.5 (−3.7 to 0.7)0.126 (1.3)11 (2.3)−1.0 (−2.9 to 0.9)0.330.21
 Abdominal pain3 (1.5)1 (0.5)1.0 (−1.4 to 3.4)0.6222 (4.6)14 (2.9)1.7 (−0.9 to 4.3)0.180.61
 Constipation7 (3.4)9 (4.5)−1.0 (−5.3 to 3.3)0.6215 (3.1)9 (1.9)1.3 (−0.9 to 3.5)0.220.22
 Diarrhea12 (5.9)6 (3.0)2.9 (−1.6 to 7.4)0.2335 (7.3)17 (3.5)3.8 (0.7 to 6.9)0.010.92
 Dyspepsia3 (1.5)5 (2.5)−1.0 (−4.2 to 2.2)0.5013 (2.7)7 (1.4)1.3 (−0.7 to 3.3)0.180.17
 Flatulence1 (0.5)0 (0.0)0.5 (−1.0 to 2.0)1.001 (0.2)2 (0.4)−0.2 (−1.1 to 0.7)1.000.25
 Nausea8 (3.9)10 (5.0)−1.0 (−5.6 to 3.5)0.6424 (5.0)20 (4.1)0.9 (−2.0 to 3.7)0.540.44
General disorders and administration site conditions
 Asthenia0 (0.0)3 (1.5)−1.5 (−3.7 to 0.7)0.1210 (2.1)7 (1.4)0.6 (−1.2 to 2.5)0.470.06
Investigations
 ALT increased9 (4.4)4 (2.0)2.4 (−1.5 to 6.4)0.2616 (3.3)5 (1.0)2.3 (0.3 to 4.4)0.020.64
 AST increased6 (3.0)4 (2.0)1.0 (−2.6 to 4.5)0.759 (1.9)7 (1.4)0.4 (−1.4 to 2.3)0.620.87
 Blood ALP increased1 (0.5)0 (0.0)0.5 (−1.0 to 2.0)1.002 (0.4)2 (0.4)0.0 (−1.0 to 1.0)1.000.37
 Blood bilirubin increased0 (0.0)0 (0.0)0 (0.0)2 (0.4)−0.4 (−1.2 to 0.4)0.50
 Blood glucose increased0 (0.0)1 (0.5)−0.5 (−2.0 to 1.0)0.500 (0.0)0 (0.0)
Musculoskeletal and connective tissue disorders
 Arthralgia7 (3.4)8 (4.0)−0.5 (−4.7 to 3.7)0.8016 (3.3)17 (3.5)−0.2 (−2.7 to 2.3)1.000.88
 Back pain9 (4.4)11 (5.5)−1.0 (−5.8 to 3.7)0.6525 (5.2)30 (6.2)−1.0 (−4.1 to 2.2)0.580.94
 Myalgia6 (3.0)1 (0.5)2.5 (−0.6 to 5.5)0.1210 (2.1)7 (1.4)0.6 (−1.2 to 2.5)0.470.21
 Pain in extremity7 (3.4)3 (1.5)2.0 (−1.6 to 5.5)0.3414 (2.9)9 (1.9)1.1 (−1.1 to 3.2)0.300.63
Nervous system disorders
 Headache13 (6.4)18 (9.0)−2.6 (−8.2 to 3.1)0.3642 (8.8)41 (8.5)0.3 (−3.4 to 4.1)0.910.36
  • Myopathy and rhabdomyolysis were not reported by any subject. REPRISE, Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD trial; SOC, system organ class; 95% CI, 95% confidence interval; ALT, alanine transaminase; AST, aspartate transaminase; ALP, alkaline phosphatase; —, numbers not suffient for analysis.

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