Clinical trial NCT02012959 (phase 3, status: terminated)
Conditions: hyponatremia
ICD codes: P74.22, E87.1
Drugs: tolvaptan
SMILES: CC1=CC=CC=C1C(=O)NC1=CC(C)=C(C=C1)C(=O)N1CCC[C@@H](O)C2=C1C=CC(Cl)=C2
Reason stopped: 
    issues with participant recruitment & enrollment which made the trial impossible or highly
    impracticable. trial termination was not due to safety reasons.
  
Eligibility criteria:

        Inclusion:

          -  Male and female participants ≥4 weeks (or ≥44 weeks adjusted gestational age) to <18
             years old

          -  Participants hospitalized with euvolemic or hypervolemic hyponatremia resistant to
             initial standard background therapy

          -  Persistent euvolemic or hypervolemic hyponatremia defined as being documented as <130
             milliequivalent (mEq)/L and present for at least 48 hours, evidenced by at least 2
             serum sodium assessments (12 hours apart)

          -  Ability to maintain adequate fluid intake (orally or intravenously)

          -  Ability to take oral medications

          -  Ability to comply with all requirements of the trial

          -  Completion of the trial-specific informed consent/assent as age appropriate

          -  Ability to commit to remain fully abstinent or practice double-barrier birth control
             as required by the trial

        Exclusion:

          -  Evidence of hypovolemia or intravascular volume depletion

          -  Serum sodium <120 mEq/L

          -  Use of potent cytochrome P450 3A4 (CYP3A4) inhibitors in participants <12 kilogram
             (kg) or moderate CYP3A4 inhibitors in participants <6 kg

          -  Lacks free access to water (inability to respond to thirst) or without intensive care
             unit level fluid monitoring and management

          -  History or current diagnosis of nephrotic syndrome

          -  Transient hyponatremia likely to resolve

          -  Hyperkalemia

          -  Estimated glomerular filtration rate <30 milliliters/minute/1.73 meters squared

          -  Acute kidney injury

          -  Severe or acute neurological symptoms requiring other intervention

          -  Prior treatment for hyponatremia with hypertonic saline within 8 hours of qualifying
             serum sodium assessments; urea, lithium, demeclocycline, conivaptan, or tolvaptan
             within 4 days of qualifying serum sodium assessments; any other treatments for the
             purpose of increasing serum sodium concurrent with dosing of trial medication

          -  Anuria or urinary outflow obstruction, unless participant is/can be catheterized

          -  History of hypersensitivity and/or idiosyncratic reaction to benzazepine or
             benzazepine derivatives

          -  Psychogenic polydipsia

          -  Uncontrolled diabetes mellitus (defined as fasting glucose >300 milligrams/deciliter)

          -  Screening liver function values >3 times the upper limit of normal

          -  Participants who have cirrhosis and meet any of the following conditions: a major GI
             bleed within the past 6 months, evidence of active bleeding, platelet count
             <50,000/microliter, or use of concomitant medications known to increase bleeding risk

          -  Hyponatremia due to the result of any medication that can safely be withdrawn or that
             is most appropriately corrected by alternative therapies

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

          -  Participants who require suspension formulation and have a Hereditary Fructose
             Intolerance

          -  Has hyponatremia that is more appropriately corrected by alternative therapies

          -  Is pregnant or currently breastfeeding

          -  Has any medical condition that could interfere with evaluation of trial objectives or
             participant safety

          -  Has participated in another investigational drug trial in the last 30 days

          -  Weighs <3 kg

          -  Unable to swallow tablets, if suspension unavailable

          -  Is deemed unsuitable for trial participation in the opinion of the investigator