A Study to Assess the Efficacy, Safety and Pharmacokinetics of Intravenous Conivaptan (Vaprisol®) in Pediatric Subjects With Euvolemic or Hypervolemic Hyponatremia
Condition: Hyponatremia
MeSH terms: Hyponatremia
Intervention: Conivaptan hydrochloride; Placebo
Intervention description: Intravenous; Intravenous
Intervention MeSH terms: Conivaptan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 4.0
Sex: All
Minimum age: 2 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Serum Sodium; Euvolemia; Hypervolemia; Vaprisol®; Conivaptan; YM087

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.
    

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 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