Study of the Safety and Effectiveness of SAMSCA® (Tolvaptan) in Children and Adolescents With Euvolemic or Hypervolemic Hyponatremia

Inclusion:

• Male and female participants ≥4 weeks (or ≥44 weeks adjusted gestational age) to <18 years old
• Participants hospitalized with euvolemic or hypervolemic hyponatremia resistant to initial standard background therapy
• Persistent euvolemic or hypervolemic hyponatremia defined as being documented as <130 milliequivalent (mEq)/L and present for at least 48 hours, evidenced by at least 2 serum sodium assessments (12 hours apart)
• Ability to maintain adequate fluid intake (orally or intravenously)
• Ability to take oral medications
• Ability to comply with all requirements of the trial
• Completion of the trial-specific informed consent/assent as age appropriate
• Ability to commit to remain fully abstinent or practice double-barrier birth control as required by the trial

Exclusion:

• Evidence of hypovolemia or intravascular volume depletion
• Serum sodium <120 mEq/L
• Use of potent cytochrome P450 3A4 (CYP3A4) inhibitors in participants <12 kilogram (kg) or moderate CYP3A4 inhibitors in participants <6 kg
• Lacks free access to water (inability to respond to thirst) or without intensive care unit level fluid monitoring and management
• History or current diagnosis of nephrotic syndrome
• Transient hyponatremia likely to resolve
• Hyperkalemia
• Estimated glomerular filtration rate <30 milliliters/minute/1.73 meters squared
• Acute kidney injury
• Severe or acute neurological symptoms requiring other intervention
• Prior treatment for hyponatremia with hypertonic saline within 8 hours of qualifying serum sodium assessments; urea, lithium, demeclocycline, conivaptan, or tolvaptan within 4 days of qualifying serum sodium assessments; any other treatments for the purpose of increasing serum sodium concurrent with dosing of trial medication
• Anuria or urinary outflow obstruction, unless participant is/can be catheterized
• History of hypersensitivity and/or idiosyncratic reaction to benzazepine or benzazepine derivatives
• Psychogenic polydipsia
• Uncontrolled diabetes mellitus (defined as fasting glucose >300 milligrams/deciliter)
• Screening liver function values >3 times the upper limit of normal
• Participants who have cirrhosis and meet any of the following conditions: a major GI bleed within the past 6 months, evidence of active bleeding, platelet count <50,000/microliter, or use of concomitant medications known to increase bleeding risk
• Hyponatremia due to the result of any medication that can safely be withdrawn or that is most appropriately corrected by alternative therapies
• History of drug or medication abuse within 3 months prior to screening or current alcohol abuse
• Participants who require suspension formulation and have a Hereditary Fructose Intolerance
• Has hyponatremia that is more appropriately corrected by alternative therapies
• Is pregnant or currently breastfeeding
• Has any medical condition that could interfere with evaluation of trial objectives or participant safety
• Has participated in another investigational drug trial in the last 30 days
• Weighs <3 kg
• Unable to swallow tablets, if suspension unavailable
• Is deemed unsuitable for trial participation in the opinion of the investigator