A Study to Assess the Efficacy, Safety and Pharmacokinetics of Intravenous Conivaptan (Vaprisol®) in Pediatric Subjects With Euvolemic or Hypervolemic Hyponatremia

A 3:1 randomization between conivaptan and placebo will be implemented and randomization
will be further stratified in a 1:1:2 ratio for age groups: 2-5 years, 6-10 years, and 11-17
years.

Subjects will need to remain hospitalized for the 48-hour Treatment Period through Hour 96
(Day 4). There will be a follow-up safety visit on Day 9 or day of hospital discharge,
whichever occurs first. There is a final follow-up phone call at Day 32 to assess if any
serious adverse events have occurred since hospital discharge.

Inclusion Criteria:

- Subject is euvolemic or hypervolemic hyponatremia upon clinical presentation

- Subject has serum sodium value ≥ 115 mEq/L (115 mmol/L) and < 130 mEq/L (130 mmol/L)
during the 24 hours preceding inclusion into the study

- Female subject of childbearing potential must have a negative serum pregnancy test
and must be premenarchal, surgically sterile or must practice a method of birth
control

Exclusion Criteria:

- Female subject is pregnant or lactating

- Subject has a body mass index (BMI) < the 3rd percentile or > the 97th percentile for
their age and stature according to the World Health Organization; Body mass
index-for-age percentiles charts for boys and girls ages 2 to 20

- Subject has clinical evidence of volume depletion, dehydration or hypovolemia

- Subject with hypovolemic hyponatremia or transient causes of hyponatremia that are
likely to resolve during the time of study participation

- Subjects with a cause of hyponatremia that is most appropriately corrected by
alternative therapies

- Subject is expected to receive emergent treatment for hyponatremia during the
treatment period of the study

- Subject has clinical evidence of hypotension

- Subject has uncontrolled hypertension > the 99th percentile for their age

- Subject has uncontrolled bradyarrhythmias or tachyarrhythmias requiring emergent
pacemaker placement or treatment

- Subject has untreated severe hypothyroidism, hyperthyroidism or adrenal insufficiency

- Subject has known urinary outflow obstruction, unless subject is, or can be
catheterized during the study

- Subject has estimated creatinine clearance < 30 mL/min during the seven days prior to
study drug administration

- Subject has alanine aminotransferase (ALT) or aspartate aminotransferase (AST)
elevations > 3 times the upper limit of normal reference range during the seven days
prior to study drug administration

- Subject has serum albumin ≤ 1.5 g/dL during the seven days prior to study drug
administration

- Subject has white blood cell count (WBC) < 3000/micro-liter documented any time
during seven days prior to study drug administration or anticipated drop in WBC to <
3000/micro-liter during the period of the study due to chemotherapy

- Subject currently has unstable hepatic function or a history of hepatic
encephalopathy, or bleeding esophageal varices within the last 3 months

- Subject has acute heart failure. Prior history of heart failure is allowed if there
are no current signs/symptoms

- Subject has a non-fasting blood glucose value ≥ 275 mg/dL

- Subject requires or is suspected to require treatment with potent inhibitors or
potent inducers of CYP3A4

- Subject was administered hypertonic saline or oral salt supplement within 24 hours
prior to study drug administration

- Subject requires the use of medications used in the treatment of Syndrome of
Inappropriate Antidiuretic Hormone Secretion (SIADH): including lithium salts, urea
or demeclocycline during the week prior to screening and throughout the study drug
treatment period

- Subject has any condition that may interfere with treatment or evaluation of safety

- Subject has received investigational therapy (including placebo) within 28 days or 5
half lives, whichever is longer