Effects of Titrated Oral Tolvaptan 15-60 mg Once Daily (QD) on Cognitive and Neurological Function in Elderly Hyponatremic Patients

Subjects will be randomized, with stratification by baseline sodium <130 or ≥ 130
mEq/L[mmol/L] to receive either tolvaptan 15 mg tablet or matching placebo tablet at doses of
15, 30 or 60 mg for 21 days. During this period, fluid restrictions should be loosened or
suspended, until the subject's response to therapy can be evaluated, typically over the first
few days of therapy. Fluid restriction may be reinstituted at any time in subjects whose
sodium fails to improve or worsens with study therapy. A forced-titration up to 60 mg of
study drug by day 3 to 7 will be based on the subject's serum sodium Subjects entering the
study with a serum sodium concentration less than 130 mEq/L[mmol/L] may be fluid restricted
if necessary at the discretion of the Investigator. Subjects should be monitored closely
during the first 24 hours of treatment for dosing titration. The total dosing duration will
be up to 21 days (plus 3 day treatment window). Subjects will return to the clinic on Day 22
(+3 days) for assessments and will complete a follow-up visit on Day 28 (+2 days).

Inclusion Criteria:

- Women and men 50 years of age or older.

- Serum Sodium ≥123 and ≤ 134 mEq/L [mmol/L]at screening and baseline.

- Subjects with serum sodium concentrations ≥118 and ≤122 mEq/L[mmol/L] at screening and
baseline may be entered into the trial based on consultation and approval from the
study medical monitor.

Exclusion Criteria:

- Conditions or history which may present a safety concern to the subject or their
offspring or extreme susceptibility to hypotension with sudden fluid loss (aquaresis).

- Hyponatremia that is acute, easily reversible, artifactual, or due to a condition not
associated with vasopressin excess or likely to respond to aquaretic therapy.

- Conditions associated with an independent imminent risk of morbidity and mortality.

- Conditions which may confound the assessment of endpoints, history of poor compliance,
participation in a clinical trial believed by the PI or Sponsor likely to confound
endpoint assessments.

- Conditions which may confound primary endpoints of cognitive function.