Effects of Tolvaptan vs Fluid Restriction in Hospitalized Subjects With Dilutional Hyponatremia

Inclusion Criteria:

- Hyponatremia in clinically euvolemic or hypervolemic states, defined as serum sodium
< 130 mEq/L prior to randomization

- Clinically significant symptoms of hyponatremia, defined as a CGI-S score between
3-6, inclusive

- Female subjects of child bearing potential who agree to remain abstinent or to
practice double-barrier forms of birth control from screening through 30 days
following first dose on IMP

Exclusion Criteria:

- Women who are pregnant or breast feeding, and females of childbearing potential who
are not using acceptable contraceptive methods (such as barrier contraceptives or
methods that result in a failure rate of less than 1%)

- Hyponatremia in hypovolemic states, defined as the presence of clinical and
historical evidence of extracellular fluid volume depletion, including but not
limited to skin turgor, orthostatic changes in blood pressure or heart rate, dry
mucous membranes, or a response to IV saline challenge

- Subjects who are likely to require prolonged hospitalization for reasons other than
hyponatremia, eg. new femoral fracture, surgeries requiring extended recovery

- Recent prior treatment for hyponatremia: hypertonic saline (including normal saline
challenge) (within 8 hours of baseline) or urea, lithium, demeclocycline, conivaptan
or tolvaptan (within 4 days of baseline). Includes any treatment, other than fluid
restriction for the purpose of increasing serum sodium.

- Hyponatremia symptoms of a severity (eg, CGI = 7) such that they require immediate
intervention with hypertonic saline; or are expected to require such therapy within
48 hours

- Causes of neurological symptoms which are attributable to psychological (psychosis),
structural (dementia of the Alzheimer's type, stroke, transient ischemic attack,
multi-infarct dementia) or other metabolic causes (eg. hyper- or hypo-: oxemia,
glycemia, calcemia, ammonemia, etc)

- Acute and transient hyponatremia associated with head trauma or severe neurological
injury (eg. stroke, subdural hematoma)or the use of recreational drugs.

- History of hyponatremia known to be due to severe, untreated hypothyroidism/adrenal
insufficiency

- Subjects with psychogenic polydipsia

- Systolic arterial blood pressure < 90 mmHg at screening

- History of hypersensitivity and/or idiosyncratic reaction to benzazepine or
benzazepine derivatives (such as benazepril), or tolvaptan

- History of drug or medication abuse within the 3 months prior to screening, or
current alcohol abuse

- Uncontrolled diabetes mellitus defined as glucose > 300 mg/dL [16.7 mmol/L]

- Current urinary tract obstruction (eg, obstructive benign prostatic hypertrophy)

- Current condition of anuria

- Serum creatinine > 3.5 mg/dL at screening

- Terminally ill or moribund condition with little chance of short-term (eg, 30 day)
survival

- Subjects whose hyponatremia is the result of any medication that can safely be
withdrawn (examples of drugs often not withdrawn include: anticonvulsants [eg,
carbamazepine] and antipsychotics [eg, haloperidol])

- Patients receiving DDAVP within 2 days of screening

- Patients with history of active variceal bleeding within the past 30 days, without
prior approval from sponsor medical monitor

- Participation in another investigational drug trial within the past 30 days