6/30/23, 2:16 AM TEMPO 3:4 Pathway Feedback Search Clinical Topics Home Studies TEMPO 3 4 TEMPO 3 4 Disease Autosomal dominant polycystic Trial question What is the role of tolvaptan in patients with autosomal dominant polycystic kidney disease? Study design Multi-center Double blinded RCT Population Characteristics of study participants 48.0% female N = 1445 52.0% male 1445 patients (699 female, 746 male) Inclusion criteria: patients, 18-50 years of age, who had autosomal dominant polycystic kidney disease with a total kidney volume 750 ml and an estimated CrCl 60 mL/min Key exclusion criteria: non-compliance with therapies, unawareness of thirst, severe allergic reactions to compounds with similar chemical structure as tolvaptan, contraindications to or interference with MRI assessments, concurrent conditions or taking therapies likely to confound endpoint assessments or prevent completion of the trial Interventions N=961 tolvaptan (lowest to highest tolerated levels in a split-dose regimen of 45/15 mg, 60/30 mg, and 90/30 mg BID) N=484 placebo (matching placebo BID) https://web.pathway.md/studies/recREUjefm5CbcNSy 1/2 6/30/23, 2:16 AM TEMPO 3:4 Pathway Primary outcome Incidence of change in the total kidney volume at 3 years 5.5 % / y 5.5 4.1 % / y 2.8 2.8 % / y 1.4 % / y Significant decrease 0.0 % / y Tolvaptan Placebo Significant decrease in the incidence of change in the total kidney volume at 3 years (2.8% / y vs. 5.5% / y; ARD -2.7, 95% CI -3.3 to -2.1) Secondary outcomes Significant decrease in the incidence of worsening kidney function (2 /100 py vs. 5 /100 py; HR 0.39, 95% CI 0.26 to 0.57) Significant decrease in the incidence of kidney pain (5 /100 py vs. 7 /100 py; HR 0.64, 95% CI 0.47 to 0.89) Significant increase in the incidence of decline in kidney function, as assessed by means of the reciprocal of the serum creatinine level (-2.61 mg/mL / y vs. -3.81 mg/mL / y; AD 1.2 mg/mL / y, 95% CI 0.62 to 1.78) Safety outcomes No significant difference in adverse events. Significant difference in adverse events leading to permanent discontinuation of the trial drug (23.0% vs. 13.8%). Conclusion In patients, 18-50 years of age, who had autosomal dominant polycystic kidney disease with a total kidney volume 750 ml and an estimated CrCl 60 mL/min, tolvaptan was superior to placebo with respect to the incidence of change in the total kidney volume at 3 years. Reference Torres VE, Chapman AB, Devuyst O et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2012 Dec 20;367(25):2407-18. Open reference URL https://web.pathway.md/studies/recREUjefm5CbcNSy 2/2