Safety, Pharmacokinetics, Tolerability and Efficacy of Tolvaptan in Children and Adolescents With ADPKD (Autosomal Dominant Polycystic Kidney Disease)
Condition: Autosomal Dominant Polycystic Kidney Disease (ADPKD)
MeSH terms: Arthrogryposis; Kidney Diseases; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant
Intervention: Tolvaptan; Tolvaptan Matching-placebo
Intervention description: Tolvaptan spray-dried, immediate release tablets; Tolvaptan matching-placebo tablets
Intervention MeSH terms: Tolvaptan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 91.0
Sex: All
Minimum age: 4 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Autosomal Dominant Polycystic Kidney Disease; ADPKD; Tolvaptan; Renal cysts; Chronic Kidney Disease; Genetic Kidney Disease

Summary:

      The primary objective of the study is to assess the long term safety of treatment with
      tolvaptan in children and adolescents with autosomal dominant polycystic kidney disease
      (ADPKD). The secondary objective is to assess the pharmacodynamics, pharmacokinetics, and
      efficacy of tolvaptan in the same participant population.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Male and female participants aged 4 to 17 years (inclusive) with a diagnosis of ADPKD
             as defined by the presence of family history and/or genetic criteria AND who have at
             least 10 renal cysts, each of which measure at least 0.5 cm, confirmed upon magnetic
             resonance imaging (MRI) inspection; participants under the age of 12 years must have
             at least 4 cysts that are at least 1 cm in size, confirmed by ultrasound.

          -  Weight ≥20 kg.

          -  Participants with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m^2
             within 31 days prior to randomization (using the Schwartz formula, eGFR = 0.413 ×
             height [cm]/serum creatinine milligrams per deciliter [mg/dL]).

          -  Independent in toileting.

          -  Ability to swallow a tablet.

        Key Exclusion Criteria:

          -  Liver function tests including aspartate aminotransferase (AST), alanine
             aminotransferase (ALT) > 1.5 × the upper limit of normal (ULN).

          -  Nocturnal enuresis.

          -  Need for chronic diuretic use.

          -  Participants with advanced diabetes (e.g., glycosylated hemoglobin >7.5, and/or
             glycosuria by dipstick, significant proteinuria, retinopathy), evidence of additional
             significant renal disease(s) (i.e., currently active glomerular nephritides), renal
             cancer, single kidney, or recent (within 6 months of screening) renal surgery or acute
             kidney injury.

          -  Participants having disorders in thirst recognition or inability to access fluids.

          -  Participants with critical electrolyte imbalances, as determined by the investigator.

          -  Participants with, or at risk of, significant hypovolemia as determined by
             investigator.

          -  Participants with clinically significant anemia, as determined by investigator.

          -  Participants 12 years of age and older having contraindications to, or interference
             with MRI assessments (e.g., ferro-magnetic prostheses, aneurysm clips, severe
             claustrophobia).

          -  Participants with a history of taking a vasopressin agonist/antagonist.

          -  Participants taking medications or having concomitant illnesses likely to confound
             endpoint assessments, including taking approved (i.e., marketed) therapies for the
             purpose of affecting polycystic kidney disease (PKD) cysts such as tolvaptan,
             vasopressin antagonists, anti-sense ribonucleic acid (RNA) therapies, rapamycin,
             sirolimus, everolimus, or somatostatin analogs (i.e., octreotide, sandostatin).

          -  Participants who have had cyst reduction surgery within 6 weeks of the screening
             visit.