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Peer-reviewedCC BY-NC-NDKidney international reports

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

  • Djalila Mekahli1,2
  • Lisa M Guay-Woodford3,4
  • Melissa A Cadnapaphornchai3
  • Larry A Greenbaum5
  • Mieczyslaw Litwin6
  • Tomas Seeman7,8
  • Ann Dandurand9,10
  • Zhen Zhang10
  • Kimberly Sikes11
  • Susan E Shoaf10
  • Franz Schaefer12
  • Pediatric Trial Investigators13
1 more authors
  • Pediatric Trial Investigators
12 affiliations
  1. 1PKD Research Group, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
  2. 2Department of Pediatric Nephrology, University Hospitals Leuven, Leuven, Belgium.
  3. 3Division of Nephrology, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadephia, Pennsylvania, USA.
  4. 4Children's National Research Institute, Washington, DC, USA.
  5. 5Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
  6. 6Children's Memorial Health Institute, Warsaw, Poland.
  7. 7Department of Pediatrics, 2nd Medical Faculty, Charles University, Prague, Czech Republic.
  8. 8Department of Pediatrics, University Hospital Ostrava and Medical Faculty of University Ostrava, Ostrava, Czech Republic.
  9. 9Stoke Therapeutics, Inc, Bedford, Massachusetts, USA.
  10. 10Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, New Jersey, USA.
  11. 11Otsuka Pharmaceutical Development & Commercialization, Inc, Rockville, Maryland, USA.
  12. 12Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany.
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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 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.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 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.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.

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Cite

BibTeXRIS
BibTeX
@article{mekahli2026clinical,
  title = {{Clinical Trial of Tolvaptan in Pediatric ADPKD: Two-Year, Open-Label Extension.}},
  author = {Djalila Mekahli and Lisa M Guay-Woodford and Melissa A Cadnapaphornchai and Larry A Greenbaum and Mieczyslaw Litwin and Tomas Seeman and Ann Dandurand and Zhen Zhang and Kimberly Sikes and Susan E Shoaf and Franz Schaefer and Pediatric Trial Investigators13 and Pediatric Trial Investigators},
  journal = {Kidney international reports},
  year = {2026},
  month = sep,
  doi = {10.1016/j.ekir.2026.107077},
  url = {https://europepmc.org/article/MED/42923342},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Clinical Trial of Tolvaptan in Pediatric ADPKD: Two-Year, Open-Label Extension.
AU  - Djalila Mekahli
AU  - Lisa M Guay-Woodford
AU  - Melissa A Cadnapaphornchai
AU  - Larry A Greenbaum
AU  - Mieczyslaw Litwin
AU  - Tomas Seeman
AU  - Ann Dandurand
AU  - Zhen Zhang
AU  - Kimberly Sikes
AU  - Susan E Shoaf
AU  - Franz Schaefer
AU  - Pediatric Trial Investigators13
AU  - Pediatric Trial Investigators
PY  - 2026
DA  - 2026/09/15
JO  - Kidney international reports
DO  - 10.1016/j.ekir.2026.107077
UR  - https://europepmc.org/article/MED/42923342
AB  - Introduction  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.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 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.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.
SN  - 2468-0249
ER  -