Table 1.
Eligibility requirements
| Inclusion criteria | |
| • Male and female subjects 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 measures at least 0.5 cm, confirmed upon MRI inspection; subjects 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 | |
| • eGFR ≥ 60 mL/min/1.73 m2 within 31 days prior to randomization (using the Schwartz formula, eGFR = 0.413 × height [cm]/serum creatinine mg/dL [15]) | |
| • Independent in toileting | |
| • Trial-specific written informed consent obtained from a parent/guardian or legally acceptable representative, as applicable for local laws, at screening, prior to the initiation of any protocol-required procedures. In addition, the subject must provide age-appropriate informed assent at screening and must be able to understand that he or she can withdraw from the trial at any time | |
| • Ability to swallow a tableta | |
| • Ability to commit to remain fully abstinent (periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] or withdrawal are not acceptable methods of contraception) or use two approved methods of birth control during the trial and for 30 days following the last dose of study drug for sexually active females of childbearing potential | |
| Exclusion criteria | |
| • Females who are breastfeeding and/or who have a positive pregnancy test result prior to receiving study drug | |
| • Liver function tests, including AST and ALT, ≥ 1.5 × upper limit of normal | |
| • Nocturnal enuresis | |
| • Need for chronic diuretic use | |
| • Subjects 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 last 6 months) renal surgery or acute kidney injury | |
| • Subjects who have known clinically significant allergic reactions to chemicals with structure similar to tolvaptan (i.e., benzazepines): benzazepril, conivaptan, fenoldopam mesylate, or mirtazapine | |
| • Subjects having disorders in thirst recognition or inability to access fluids | |
| • Subjects who have bladder dysfunction and/or difficulty voiding | |
| • Subjects with critical electrolyte imbalances, as determined by the investigator | |
| • Subjects with or at risk of significant hypovolemia, as determined by investigator | |
| • Subjects with a history of substance abuse (within the last 6 months) | |
| • Subjects 12 years of age and older having contraindications to, or interference with, MRI assessments (e.g., ferro-magnetic prostheses, aneurysm clips, severe claustrophobia) | |
| • Subjects taking a vasopressin agonist (e.g., desmopressin) | |
| • Subjects with a history of persistent noncompliance with antihypertensive or other important medical therapy | |
| • Subjects 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 cysts such as tolvaptan, vasopressin antagonists, anti-sense RNA therapies, rapamycin, sirolimus, everolimus, or somatostatin analogs (i.e., octreotide, sandostatin) | |
| • Has any medical condition that, in the opinion of the investigator, could interfere with evaluation of the trial objectives or safety of the subjects | |
| • Is deemed unsuitable for trial participation in the opinion of the investigator | |
| • Subjects who received any investigational agent in a clinical trial within 30 days prior to screening | |
| • Subjects who have a known lactose intolerance | |
| • Subjects who have had cyst reduction surgery within 6 weeks of the screening visit |
ADPKD autosomal dominant polycystic kidney disease, ALT alanine aminotransferase, AST aspartate aminotransferase, eGFR estimated glomerular filtration rate, MRI magnetic resonance imaging, RNA ribonucleic acid
aMust also meet health authority/ethics committee age restrictions on tablet use (if applicable)