a study to assess the efficacy, safety and pharmacokinetics of intravenous conivaptan (vaprisol®) in pediatric subjects with euvolemic or hypervolemic hyponatremia

Conditions: Hyponatremia

Summary: the objective of this study is to evaluate the efficacy, safety and pharmacokinetics of intravenous conivaptan in pediatric subjects with abnormally low concentration of sodium in blood.

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.

Eligibility criteria:
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 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

Keywords: serum sodium euvolemia hypervolemia vaprisol® conivaptan ym087