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