Table 4.

Investigator-reported treatment-emergent adverse events under the “hepatic failure, fibrosis and cirrhosis, and other liver-damage-related conditions” standardized Medical Dictionary for Regulatory Activities query by Medical Dictionary for Regulatory Activities preferred term

SubjectPreferred TermPrior Treatment SubgroupSerious (Yes/No), Relatedness to Study Drug per InvestigatorAdjudicated Yes/NoRelatedness to Study Drug per Hepatic Adjudication CommitteeAction Regarding Study DrugOutcome
1AscitesREPRISE TOLNo, not relatedNoContinuedNot recovered/not resolved
AscitesREPRISE TOLNo, not relatedNoContinuedNot recovered/not resolved
2AscitesaREPRISE TOLYes, not relatedYesUnlikelyContinuedRecovered/resolved
AscitesaREPRISE TOLYes, not relatedYesUnlikelyDiscontinuedRecovered/resolved
3AscitesREPRISE TOLNo, not relatedYesUnlikelyContinuedNot recovered/not resolved
Portal hypertensionREPRISE TOLNo, not relatedNoContinuedNot recovered/not resolved
4AscitesREPRISE PLCYes, not relatedYesUnlikelyDiscontinuedRecovered/resolved
5Portal hypertensive gastropathyTEMPO 4:4 TOLNo, not relatedNoContinuedRecovered/resolved
6Varices esophagealTEMPO 4:4 TOLNo, not relatedNoContinuedNot recovered/not resolved
Portal hypertensionTEMPO 4:4 TOLNo, not relatedNoContinuedNot recovered/not resolved
7Drug-induced liver injuryREPRISE TOLNo, relatedYesPossibleDiscontinuedRecovered/resolved
8Hepatic steatosisTEMPO 4:4 TOLNo, not relatedNoContinuedNot recovered/not resolved
9Liver injuryTEMPO 4:4 TOLNo, not relatedYesUnlikelyDiscontinuedRecovered/resolved
10Nonalcoholic fatty liverTEMPO 4:4 TOLNo, not relatedYesPossibleNot applicablebNot recovered/not resolved
  • REPRISE, Replicating Evidence of Preserved Renal Function: An Investigation of Tolvaptan Safety and Efficacy in Autosomal Dominant Polycystic Kidney Disease; TOL, tolvaptan; PLC, placebo; TEMPO, Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes.

  • a Two cases were recorded in the clinical database because the event severity changed from moderate to severe. The Hepatic Adjudication Committee adjudicated the two events together.

  • b Drug had been withdrawn prior to the event of nonalcoholic fatty liver, due to an earlier event of alanine aminotransferase increasing.