Clinical Trial of Tolvaptan in Pediatric ADPKD: Two-Year, Open-Label Extension

Tolvaptan is indicated for adults with autosomal dominant polycystic kidney disease (ADPKD) at increased risk of rapid progression. Pharmacodynamic activity and acceptable safety and tolerability were demonstrated in a 1-year, randomized, placebo-controlled trial in children and adolescents with ADPKD (Phase A of a 2-part, phase-3b study [NCT02964273]). Here, the 2-year, open-label extension (Phase B) is reported.

Phase A participants could enter Phase B if they had not experienced adverse events requiring discontinuation. All Phase B participants received tolvaptan, titrated based on body weight and tolerability. Outcomes included safety, tolerability, kidney function, height-adjusted total kidney volume (htTKV), and health-related quality of life (HRQoL).

Of 84 Phase A completers, 81 enrolled in Phase B. No liver enzyme elevations observed in either phase met criteria for drug-induced liver injury. The previous placebo group experienced more aquaresis-related (48.7% vs. 14.3%) and dehydration-related (28.2% vs. 14.3%) adverse events than the previous tolvaptan group in Phase B. Tolerability was favorable, with HRQoL outcomes indicating high functioning in both the trial phases. Estimated glomerular filtration rate (eGFR) remained stable in the tolvaptan arm and decreased in the placebo arm of Phase A (annual slope in ml/min per 1.73 m² of 2.4 and -2.2, respectively [P = 0.04]), with similar slopes of decline for both arms of Phase B (-1.3 in the prior tolvaptan arm and -2.1 in the prior placebo arm [P = 0.54]). htTKV growth was slowest during the first year of tolvaptan treatment.

Tolvaptan-related safety and overall HRQoL remained favorable, and kidney function was stable in this 2-year extension. The slowest htTKV growth occurred during year 1 of tolvaptan treatment.