Year: 2026
Type: article
Abstract: Introduction Tolvaptan is indicated for adults with autosomal dominant polycystic kidney disease (ADPKD) at increased risk of rapid progression. Pharmacodynamic activity and acceptable safety/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. Methods 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). Results 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 prior placebo group experienced more aquaresis-related (48.7% versus 14.3%) and dehydration-related (28.2% versus 14.3%) adverse events than the prior tolvaptan group in Phase B. Tolerability was favorable, with HRQoL outcomes indicating high functioning in both trial phases. eGFR remained stable in the tolvaptan arm and decreased in the placebo arm of Phase A (annual slope in mL/min/1.73 m 2 of 2.4 and -2.2, respectively [ P =0.04]), with similar slopes of decline for both arms of Phase B (-1.3 prior tolvaptan and -2.1 prior placebo [ P =0.54]). htTKV growth was slowest during the first year of tolvaptan treatment. Conclusion 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.
Source: Kidney International Reports
Authors: Djalila Mekahli, Lisa M. Guay-Woodford, Melissa A. Cadnapaphornchai, Larry A. Greenbaum, Mieczyslaw Litwin, Tomas Seeman, Ann Dandurand, Zhen Zhang, Kimberly Sikes, Susan E. Shoaf, Franz Schaefer, Johan Vande Walle, Djalila Mekahli, Nathalie Godefroid, Marie-Sophie Ghuysen, Elke Wüehl, Max Christoph Liebau, Matthias Zirngibl, Michaela Geßner, Heiko Billing, Jens Drube, Lars Pape, Raphael-Sebastian Schild, Jun Oh, Annett Blaser, Katalin Dittrich, Ciro Esposito, Giovanni Montini, Giovanna Capolongo, Giovambattista Capasso, Carmine Pecoraro, Detlef Bockenhauer, Cand Med, Mohan Shenoy, Nicholas Webb, Andrew Lunn, Larissa Kerecuk, Mordi Muorah, Manish Sinha
Institutions: Universitair Ziekenhuis Leuven, KU Leuven, Children's Hospital of Philadelphia, Children's National, University of Pennsylvania, Emory University, Children's Healthcare of Atlanta, Children's Memorial Health Institute, Charles University, University Hospital Ostrava, Otsuka (United States), Stoke Therapeutics, Inc. (United States), Otsuka Pharmaceutical Development & Commercialization, Inc. (United States)
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,800
OpenAlex ID: W7213244870