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Eur J Pediatr. 2019 May 3. doi: 10.1007/s00431-019-03384-x. [Epub ahead of print]

Tolvaptan use in children and adolescents with autosomal dominant polycystic kidney disease: rationale and design of a two-part, randomized, double-blind, placebo-controlled trial.

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Division of Pediatric Nephrology, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany.
Department of Pediatric Nephrology, University Hospitals Leuven, Herestraat 49, B-3000, Leuven, Belgium.
PKD Research Group, Department of Development and Regeneration, KU Leuven, Herestraat 49, B-3000, Leuven, Belgium.
Pediatric Nephrology, Bambino Gesù Children's Hospital, Piazza Sant' Onofrio 4, 00165, Rome, Italy.
Regional Paediatric Nephro-Urology Unit, Southampton Children's Hospital, Tremona Road, Southampton, SO16 6YD, UK.
UCL Department of Renal Medicine, UCL Medical School, Rowland Hill Street, London, NW3 2PF, UK.
Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, WC1N 3JH, UK.
Rocky Mountain Pediatric Kidney Center, Rocky Mountain Hospital for Children at Presbyterian/St. Luke's Medical Center, 2055 High Street, Suite 270, Denver, CO, 80205, USA.
Otsuka Pharmaceutical Development & Commercialization, 2440 Research Boulevard, Rockville, MD, 20850, USA.
Otsuka Pharmaceutical Development & Commercialization, 508 Carnegie Center Drive, Princeton, NJ, 08540, USA.


This report describes the rationale and design of a study assessing tolvaptan in children with autosomal dominant polycystic kidney disease (ADPKD). Phase A is a 1-year, randomized, double-blind, placebo-controlled, multicenter trial. Phase B is a 2-year, open-label extension. The target population is at least 60 children aged 12-17 years, diagnosed by family history and/or genetic criteria and the presence of ≥ 10 renal cysts, each ≥ 0.5 cm on magnetic resonance imaging. Subjects will be allocated into 4 groups: females 15-17 years; females 12-14 years; males 15-17 years; and males 12-14 years. Up to 40 subjects aged 4-11 years may also enroll, provided they meet the entry criteria. Weight-adjusted tolvaptan doses, titrated once to achieve a tolerated maintenance dose, and matching placebo will be administered twice-daily. Assessments include spot urine osmolality and specific gravity (co-primary endpoints), height-adjusted total kidney volume, estimated glomerular filtration rate, pharmacodynamic parameters (urine volume, fluid intake and fluid balance, serum sodium, serum creatinine, free water clearance), pharmacokinetic parameters, safety (aquaretic adverse events, changes from baseline in creatinine, vital signs, laboratory values including liver function tests), and generic pediatric quality of life assessments.Conclusion: This will be the first clinical study to evaluate tolvaptan in pediatric ADPKD. What is Known: • Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder causing the development of cysts that impede kidney function over time and eventually induce renal failure • There are few data on the effects of tolvaptan, the only treatment approved for adults to slow disease progression, in pediatric ADPKD patients with early-stage disease What is New: • A phase 3, placebo-controlled study is evaluating tolvaptan over 3 years in children and adolescents with ADPKD • This study is designed to account for challenges of tolvaptan dosing and outcome assessment specific to the pediatric population.


Autosomal dominant polycystic kidney disease; Clinical trial; Nephrology; Pharmacotherapy; Tolvaptan


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