A Phase 3b, Multicenter, Extension Follow-up Trial to Evaluate the Safety of Children and Adolescent Subjects With Euvolemic or Hypervolemic Hyponatremia Who Have Previously Participated in a Trial of Tolvapta

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 140

Inclusion Criteria

1. Enrollment in one of the previous tolvaptan pediatric trials for hyponatremia (ie, Trial 156-08-276, 156-13-207, or 156-12-205).
2. Trial-specific written informed consent/assent obtained from a parent/guardian or legally acceptable representative, as applicable for local laws, prior to the initiation of any protocol-required procedures. In addition, the subject must provide informed assent at baseline and must be able to understand that he or she can withdraw from the trial at any time. All informed consent/assent procedures must be in accordance with the trial center?s IRB/IEC and local regulatory requirements.
3. Ability to comply with all requirements of the trial
4. Willingness to be clinically followed for 6 months
Are the trial subjects under 18? yes
Number of subjects for this age range: 140
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

Safety follow-up component of this trial: There are no exclusion criteria.
Optional Tolvaptan Treatment Component of this trial:
1. Has evidence of hypovolemia or intravascular volume depletion (eg, hypotension, clinical evidence of volume depletion, response to saline challenge); if the subject has systolic blood pressure or heart rate outside of the normal range for that age volume status should be specifically clinically assessed to rule out volume depletion.
2. Has serum sodium < 120 mEq/L (mmol/L), with or without associated neurologic impairment (ie, symptoms such as apathy, confusion, or seizures)
3. Use of potent CYP3A4 inhibitors in subjects ? 50 kg or moderate CYP3A4 inhibitors in subjects < 20 kg
4. Lacks free access to water (inability to respond to thirst) or without ICU-level fluid monitoring and management
5. Has a history or current diagnosis of nephrotic syndrome
6. Has transient hyponatremia likely to resolve (eg, head trauma or post-operative state)
7. Has hyperkalemia defined as serum potassium above the ULN for the appropriate pediatric age range
8. Has eGFR < 30 mL/min/1.73 m2 calculated by the following equation:
eGFR (mL/min/1.73 m2) = 0.413 x height (cm)/serum creatinine (mg/dL)
9. Has AKI defined as:
- Increase in serum creatinine by ? 0.3 mg/dL (? 26.5 µmol/L) within 48 hours; or
- Increase in serum creatinine to ? 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or
- Urine volume < 0.5 mL/kg/h for 6 hours
10. Has severe or acute neurological symptoms requiring other intervention (eg, hyperemesis, obtundation, seizures)
11. Has had treatment for hyponatremia with:
- Hypertonic saline (including normal saline challenge) within 8 hours of qualifying serum sodium assessments;
- Urea, lithium, demeclocycline, conivaptan, or tolvaptan within 4 days of qualifying serum sodium assessments;
- Other treatment for the purpose of increasing serum sodium concurrent with dosing of trial medication
12. Has anuria or urinary outflow obstruction, unless the subject is, or can be, catheterized during the trial
13. Has a history of drug or medication abuse within 3 months prior to the pretreatment visit or current alcohol abuse
14. Has a history of hypersensitivity and/or idiosyncratic reaction to benzazepine or benzazepine derivatives (such as benazepril)
15. Has psychogenic polydipsia (subjects with other psychiatric illness may be included per medical monitor approval)
16. Has uncontrolled diabetes mellitus, defined as fasting glucose > 300 mg/dL (16.7 mEq/L [mmol/L])
17. Has screening liver function values > 3 x ULN. An IRE form will be completed if the subject is a potential Hy?s Law case (any increase of AST or ALT ? 2 X ULN or baseline value with an increase
in BT ? 2 X ULN or baseline value)
18. Has deficient coagulation (eg, cirrhotic at risk of GI bleed), including subjects who meet any of the following criteria: a major GI bleed within the past 6 months, evidence of active bleeding (eg,
epistaxis, petechiae/purpura, hematuria, or hematochezia), platelet count < 50,000/µL, or use of concomitant medications known to increase bleeding risk
19. Has hyponatremia due to the result of any medication that can safely be withdrawn (eg, thiazide diuretics)
20. Has hyponatremia (eg, hyponatremia in the setting of adrenal insufficiency, untreated hypothyroidism, or hypotonic fluid administration) that is most appropriately corrected by alternative therapies
21. Is currently pregnant or b

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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