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Abstract: SA-PO479

Tolvaptan (TLV) in Children and Adolescents with Autosomal Dominant Polycystic Kidney Disease (ADPKD): Design of a Two-Part, Randomized, Double-Blind, Placebo (PBO)-Controlled Trial

Session Information

  • ADPKD: Clinical Studies
    October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidney

  • 1001 Genetic Diseases of the Kidney: Cystic


  • Schaefer, Franz S., University of Heidelberg, Heidelberg, BW, Germany
  • Mekahli, Djalila, KULeuven, Leuven, Belgium
  • Emma, Francesco, Bambino Gesu Children's Hospital, Rome, Rome, Italy
  • Gilbert, Rodney David, Southampton Children''s Hospital, Southampton, United Kingdom
  • Bockenhauer, Detlef, University College London, London, United Kingdom
  • Cadnapaphornchai, Melissa A., Rocky Mountain Pediatric Kidney Center, Rocky Mountain Hospital for Children at Presbyterian St. Luke's Medical Center, Denver, Colorado, United States
  • Shi, Lily, Otsuka Pharmaceutical Development & Commercialization, Rockville, Maryland, United States
  • Dandurand, Ann, Otsuka Pharmaceutical Development & Commercialization, Rockville, Maryland, United States
  • Watkin, Suzanne, Otsuka Pharmaceutical Development & Commercialization, Rockville, Maryland, United States
  • Shoaf, Susan E., Otsuka Pharmaceutical Development & Commercialization, Rockville, Maryland, United States

TLV slows ADPKD progression in adults; its value in affected children and adolescents remains unknown. The first trial to assess TLV in pediatric ADPKD is currently ongoing (NCT02964273). We present the unique features of the trial population and its design.


This multicenter trial comprises two phases: Phase A is one year, randomized, double-blind, and PBO-controlled, Phase B is a two year open-label extension for subjects who completed Phase A. As formal diagnostic criteria for pediatric ADPKD are not developed, an advisory panel agreed eligibility would be based on family history/genetic criteria and would require ≥ 10 renal cysts measuring ≥ 0.5 cm on MRI to warrant treatment. Subjects (n=60) are allocated into 4 groups by gender and age (12–14y;15–17y). Subjects aged 4–11y may enroll. TLV is initiated at a weight-adjusted split dose ≤ 67% of the adult starting dose to allow for acclimation to excess diuresis; TLV is up-titrated after 1 wk to approximate the weight-adjusted starting dose for adults. Down-titration is permitted per tolerance. Assessments include spot urine osmolality and specific gravity (co-primary endpoints), total kidney volume, eGFR, PD parameters (urine volume, fluid intake and fluid balance, serum sodium, serum creatinine, and free water clearance), PK parameters, and generic pediatric QoL assessments. Safety parameters include AEs, changes in creatinine, vital signs, and lab values. Subjects are tested for ALT/AST, alkaline phosphatase and total bilirubin during screening and for ALT/AST monthly during treatment. Liver function tests are reviewed by investigators, and by independent hepatic adjudication and independent data monitoring committees. Stringent monitoring and intervention rules ensure rapid response to any potential hepatic signals.




Kidney enlargement is continuous in ADPKD; cysts expand years before a reduction in GFR is apparent. This trial assesses the tolerability of TLV and begins to test the hypothesis that early treatment with a disease-modifying agent might be beneficial. Available interim data will be presented.


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