Weekly issue 2026-W43 ·
Clinical Trial of Tolvaptan in Pediatric ADPKD: Two-Year, Open-Label Extension
Plain language
Tolvaptan is approved for adults with autosomal dominant polycystic kidney disease (ADPKD) at high risk of rapid progression, and a two-part Phase 3b trial (NCT02964273) has been studying it in children and adolescents. After a 1-year randomized comparison against placebo (Phase A), 81 of the 84 young participants entered a 2-year open-label extension (Phase B) in which everyone received weight-adjusted tolvaptan. Over those two additional years, no participant developed drug-induced liver injury, quality-of-life scores remained high, and kidney function stayed broadly stable in both those continuing tolvaptan and those switching from placebo. Thirst- and urination-related side effects were more common in the group starting tolvaptan for the first time in Phase B.
Clinical note
Phase 3b, 2-year open-label extension (Phase B of NCT02964273; Kidney Int Rep) in paediatric ADPKD: 81 of 84 Phase A completers enrolled and received weight- and tolerability-titrated tolvaptan. No liver enzyme elevations in either phase met drug-induced liver injury criteria. Participants switching from Phase A placebo to Phase B tolvaptan had more aquaresis-related (48.7% vs 14.3%) and dehydration-related (28.2% vs 14.3%) adverse events than those continuing tolvaptan; HRQoL remained high across both phases. Annual eGFR slope had differed in Phase A (+2.4 vs -2.2 mL/min/1.73 m²/year for tolvaptan vs placebo, p = 0.04) and was similar between arms during Phase B (-1.3 vs -2.1 mL/min/1.73 m²/year for prior-tolvaptan vs prior-placebo, p = 0.54); htTKV growth was slowest during year 1 of tolvaptan exposure.
Question for your next visit
How should a child or teenager with ADPKD be monitored over time, and what treatments or trials are appropriate at their age?