Euvolemic or Hypervolemic Hyponatremia MedDRA version: 20.0 Level: LLT Classification code 10021038 Term: Hyponatremia System Organ Class: 100000004861
Conditions
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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 Eligibility criteria for optional treatment component: 1. Male or female subjects = 4 weeks (or = 44 weeks adjusted gestational age to =65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: Safety follow-up component of this trial: There are no exclusion criteria. Ineligibility criteria for 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 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 Has hyponatremia due to the result of any medication that can safely be withdrawn (eg, thiazide diuretics) 20.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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: For all subjects: To evaluate the post-treatment safety follow-up of children and adolescent subjects with dilutional (euvolemic or hypervolemic) hyponatremia who have previously participated in a trial of titrated oral investigational medicinal product (IMP [tolvaptan in Trial 156-08-276, tolvaptan or placebo in Trials 156-13-207 and 156-12-205]). For subjects who receive tolvaptan: To demonstrate that tolvaptan safely and effectively achieves and maintains increased serum sodium concentrations in children and adolescent subjects with dilutional (euvolemic or hypervolemic) hyponatremia when used for both multiple short-term treatments and/or longer chronic treatments.;Secondary Objective: Not applicable;Primary end point(s): Change from baseline in serum sodium while tolvaptan is being administered.;Timepoint(s) of evaluation of this end point: Change from baseline in serum sodium while tolvaptan is being administered by Visit so there will be several primary end-points depending on the number of visits that the subject will have. Hence, the change in serum sodium at each visit will be measured and the mean value will be the primary end point. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Optional Tolvaptan Treatment Component: 1. Percentage of subjects who require rescue therapy while on tolvaptan treatment 2. Percentage of subjects requiring continuation of tolvaptan following 30 days of treatment 3. Percentage of subjects with overly rapid correction in serum sodium (=12 mmol/L in 24 hours after the first dose at introduction or reintroduction of tolvaptan) 4. Changes from baseline in ALT, AST and BT. Core Safety Follow up Component: 1. Frequency of AE reports 2. Change from baseline in QoL assessments 3. Change from baseline in growth percentiles -for body weight - body height 4. Tanner Staging progression score - Change from baseline in serum sodium by visit ;Timepoint(s) of evaluation of this end point: Optional Tolvaptan Treatment Component: 1. Percentage of subjects who require rescue therapy while on tolvaptan treatment (Evaluation time point: all trial duration) 2. Percentage of subjects requiring continuation of tolvaptan following 30 days of treatment (Evaluation timepoint after 30 days of treatment minimum) 3. Percentage of subjects with overly rapid correction in serum sodium (=12 mmol/L in 24 hours after the first dose at introduction or reintroduction of tolvaptan) (Evaluation timepoint: Any visit with this increase) 4. Changes from baseline in ALT, AST and BT (Evaluation timepoint: Each visit). Core Safety Followup Component: Evaluation timepoint for most of the secondary endpoints is Any Visit. For more details, please see Appendix 5 of current protocol amendment1. | — |
Countries
Belgium, Canada, Czech Republic, Germany, Italy, Poland, Romania, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactSuzanne Watkin
Otsuka Pharmaceutical Development & Commercialization, Inc.
Outcome results
None listed