HyponatremiaPhase 3NCT02442674
A Trial of Tolvaptan in Children and Adolescent Subjects With Euvolemic and Hypervolemic Hyponatremia
A Phase 3 study testing Tolvaptan in people with Hyponatremia, run by Otsuka Pharmaceutical Development & Commercialization, Inc..
Trial summary
The purpose of this trial is to demonstrate that tolvaptan effectively and safely increases and maintains serum sodium concentrations in children and adolescent subjects with euvolemic or hypervolemic hyponatremia. Read more about this study
- Who is it for?
- Ages 4 to 17 years
- Conditions the study is for
- Hyponatremia
- What is being tested?
- Tolvaptan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Nov 2015to 22 Jun 2017
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male and female subjects ≥ 4 years of age (or per local Health Authority age restriction) to < 18 years old and ≥ 10kg
- Subjects hospitalized with euvolemic or hypervolemic hyponatremia resistant to initial standard background therapy (including fluid restriction and excluding a vasopressin antagonist) and who are deemed by the investigator as likely to benefit from a therapy that raises serum sodium levels
- Persistent euvolemic or hypervolemic hyponatremia defined as being documented as present for at least 48 hours, evidenced by at least 2 serum sodium assessments < 130 mmol/L drawn at least 12 hours apart (these values can be documented using historical values previously obtained per standard of care); a third (STAT) serum sodium assessment < 130 mmol/L, which will serve as the baseline value for efficacy endpoints, is to be obtained within 2-4 hours prior to the final trial qualification and the first dose of IMP
- Ability to swallow tablets
- Ability to maintain adequate fluid intake whether orally or via IV support with adequate monitoring
- Ability to comply with all requirements of the trial
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- Trial-specific written informed consent/assent obtained from a parent/legal guardian or legally acceptable representative, as applicable per age of subject or local laws, prior to the initiation of any protocol required procedures. In addition, the subject as required by local laws must provide informed assent at Screening 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
- Ability to commit to remain fully abstinent (periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] or withdrawal are not acceptable methods of contraception) or practice double-barrier birth control during the trial and for 30 days following the last dose of IMP for sexually active females of childbearing potential
Who cannot join
- 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
- Has serum sodium < 120 mmol/L, with or without associated neurologic impairment (ie, symptoms such as apathy, confusion, or seizures)
- Subjects ≤ 50 kg taking potent CYP3A4 inhibitors or subjects < 20 kg taking moderate CYP3A4 inhibitors within 72 hours prior to dosing
- Lacks free access to water (inability to respond to thirst) or without ICU-level fluid monitoring and management
- Has a history or current diagnosis of nephrotic syndrome
- Has transient hyponatremia likely to resolve (eg, head trauma or post-operative state)
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- Has hyperkalemia defined as serum potassium above the ULN for the appropriate pediatric age range
- 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)
- Has AKI from recent medical history 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
- Has severe or acute neurological symptoms requiring other intervention (eg, hyperemesis, obtundation, seizures)
- 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 IMP
- Has anuria or urinary outflow obstruction, unless the subject is, or can be, catheterized during the trial
- Has a history of drug or medication abuse within 3 months prior to Screening or current alcohol abuse
- Has a history of hypersensitivity and/or idiosyncratic reaction to benzazepine or benzazepine derivatives (such as benazepril)
- Has psychogenic polydipsia (subjects with other psychiatric illness may be included per medical monitor approval)
- Has uncontrolled diabetes mellitus, defined as fasting glucose > 300 mg/dL (16.7 mmol/L)
- Has screening liver function values (ALT/AST) > 3 x ULN
- Has cirrhosis and meets any of the following conditions: 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
- Has hyponatremia due to the result of any medication that can safely be withdrawn (eg, thiazide diuretics)
- Has hyponatremia (eg, hyponatremia in the setting of adrenal insufficiency, untreated hypothyroidism, or hypotonic fluid administration) that is most appropriately corrected by alternative therapies
- Is currently pregnant or breastfeeding
- Has any medical condition that, in the opinion of the investigator, could interfere with evaluation of the trial objectives or safety of the subjects.
- Is deemed unsuitable for trial participation in the opinion of the investigator
- Participation in another investigational drug trial within the past 30 days, without prior approval from the sponsor medical monitor
- Subjects < 4 years of age or per local Health Authority age restriction, weight < 10 kg, or who are unable to swallow tablets are excluded until an alternate formulation becomes available
About this study
Official title: A Pilot Phase 3b,Multicenter,Randomized,Double-blind,Placebo-controlled Trial of the Safety,Efficacy,and Pharmacokinetics of Titrated Oral SAMSCA®(Tolvaptan) in Children and Adolescent Subjects With Euvolemic or Hypervolemic Hyponatremia
The purpose of this trial is to demonstrate that tolvaptan effectively and safely increases and maintains serum sodium concentrations in children and adolescent subjects with euvolemic or hypervolemic hyponatremia.
Read the detailed description
The purpose of the study is to also assess tolvaptan's pharmacokinetics (PK) and its effect on fluid balance in children and adolescent subjects with euvolemic or hypervolemic hyponatremia. Subjects who are diagnosed with euvolemic or hypervolemic hyponatremia (serum sodium < 130 mEq/L [mmol/L]) that persists despite initial standard background therapy (eg, including fluid restriction) are eligible to be screened for participation in this trial. Subjects who demonstrate prior resistance to vasopressin antagonist therapy will be excluded. All potential subjects must be deemed by the investigator as likely to benefit from a therapy that raises serum sodium levels.
Subjects will be required to be in a hospital setting during initiation or titration of tolvaptan. Overall, in this trial, subjects will undergo treatment with tolvaptan or placebo for 30 (+2) days and a post-last dose follow-up phase of 14 days.
- Conditions
- Hyponatremia
- Being tested
- Tolvaptan, Placebo
- Keywords
- Hyponatremia, Euvolemic, Hypervolemic, Serum sodium, Dilutional hyponatremia, Electrolyte abnormality, Electrolyte imbalance, Metabolic disease, Water-Electrolyte Imbalance
- Medical subject headings
- Hyponatremia, Metabolic Diseases, Water-Electrolyte Imbalance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TolvaptanDrug
Also called SAMSCA
Tolvaptan 3.75-, 7.5-, 15-, and 30-mg Tablets.
Dosage: Depending on age, weight and serum sodium response:
Tablet (3.75 mg - 60 mg daily) Frequency: Once daily Duration: 30 (+2) days
PlaceboOther
Placebo tablet matching active drug
| Study group | Role | What they receive |
|---|---|---|
| Tolvaptan | Active comparator | Tolvaptan (3.75 mg, 7.5 mg, 15 mg, 30 mg, 60 mg dose daily depending on age and weight) Receives: Drug: Tolvaptan |
| Placebo | Placebo comparator | Placebo tablet matching active drug Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in serum sodium concentration
The average daily area under the curve (AUC) of change from baseline in serum sodium level up to Day 4 within the double-blind treatment period.
Measured: Daily up to day 4
Secondary outcomes (9)
Change of average daily AUC from baseline at each visit in serum sodium level.
Measured: Daily up to Day 30
Change from baseline in serum sodium concentration at Day 4.
Measured: Day 4
Change from baseline in serum sodium concentration at Day 30.
Measured: Daily up to Day 30
Percentage of subjects who require rescue therapy or fluid restriction at any time during the double-blind treatment period.
Measured: Daily up to Day 30
Changes from baseline in ALT, AST and Total Bilirubin
Measured: Daily up to Day 30
Clinically significant changes in vital signs.
Measured: Daily up to Day 30
Incidence of dehydration AEs.
Measured: Daily up to Day 30
Tanner staging progression score (at 30 days)
Measured: Daily up to Day 30
Percentage of subjects with overly rapid correction in serum sodium ( ≥ 12 mmol/L in 24 hours).
Measured: Daily up to Day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2015 (estimated)
- Study startNov 2015
- Primary completion22 Jun 2017
- Study completion22 Jun 2017
Why it stopped: Trial withdrawn due to inability to meet the trial objectives (Pilot).
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HyponatremiaStudies of the same condition, open and under way.
- More trials run by Otsuka Pharmaceutical Development & Commercialization, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ann Dandurand, MD, Study director, Otsuka Pharmaceutical Development & Commercialization, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02442674
- Sponsor's protocol ID
- 156-13-207
- Status last verified
- Jul 2017
- First submitted
- 8 May 2015
- Last updated
- 31 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Phase 3b,Multicenter,Randomized,Double-blind,Placebo-controlled Trial of the Safety,Efficacy,and Pharmacokinetics of Titrated Oral SAMSCA®(Tolvaptan) in Children and Adolescent Subjects With Euvolemic or Hypervolemic Hyponatremia
- ClinicalTrials.gov ID
- NCT02442674
- Acronym / sponsor ID
- 156-13-207
- Conditions
- Hyponatremia
- Keywords
- Hyponatremia, Euvolemic, Hypervolemic, Serum sodium, Dilutional hyponatremia, Electrolyte abnormality, Electrolyte imbalance, Metabolic disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Trial withdrawn due to inability to meet the trial objectives (Pilot).
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Study start
- Nov 2015
- Primary completion
- 22 Jun 2017 (actual)
- Study completion
- 22 Jun 2017 (actual)
- First posted
- 13 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this trial is to demonstrate that tolvaptan effectively and safely increases and maintains serum sodium concentrations in children and adolescent subjects with euvolemic or hypervolemic hyponatremia.
Detailed description
The purpose of the study is to also assess tolvaptan's pharmacokinetics (PK) and its effect on fluid balance in children and adolescent subjects with euvolemic or hypervolemic hyponatremia. Subjects who are diagnosed with euvolemic or hypervolemic hyponatremia (serum sodium < 130 mEq/L [mmol/L]) that persists despite initial standard background therapy (eg, including fluid restriction) are eligible to be screened for participation in this trial. Subjects who demonstrate prior resistance to vasopressin antagonist therapy will be excluded. All potential subjects must be deemed by the investigator as likely to benefit from a therapy that raises serum sodium levels.
Subjects will be required to be in a hospital setting during initiation or titration of tolvaptan. Overall, in this trial, subjects will undergo treatment with tolvaptan or placebo for 30 (+2) days and a post-last dose follow-up phase of 14 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tolvaptan | Active comparator | Drug: TolvaptanTolvaptan (3.75 mg, 7.5 mg, 15 mg, 30 mg, 60 mg dose daily depending on age and weight) |
| Placebo | Placebo comparator | Other: PlaceboPlacebo tablet matching active drug |
Who may qualify
- Ages
- 4 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- Male and female subjects ≥ 4 years of age (or per local Health Authority age restriction) to < 18 years old and ≥ 10kg
- Subjects hospitalized with euvolemic or hypervolemic hyponatremia resistant to initial standard background therapy (including fluid restriction and excluding a vasopressin antagonist) and who are deemed by the investigator as likely to benefit from a therapy that raises serum sodium levels
- Persistent euvolemic or hypervolemic hyponatremia defined as being documented as present for at least 48 hours, evidenced by at least 2 serum sodium assessments < 130 mmol/L drawn at least 12 hours apart (these values can be documented using historical values previously obtained per standard of care); a third (STAT) serum sodium assessment < 130 mmol/L, which will serve as the baseline value for efficacy endpoints, is to be obtained within 2-4 hours prior to the final trial qualification and the first dose of IMP
- Ability to swallow tablets
- Ability to maintain adequate fluid intake whether orally or via IV support with adequate monitoring
Key exclusion criteria (32 listed)
- 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
- Has serum sodium < 120 mmol/L, with or without associated neurologic impairment (ie, symptoms such as apathy, confusion, or seizures)
- Subjects ≤ 50 kg taking potent CYP3A4 inhibitors or subjects < 20 kg taking moderate CYP3A4 inhibitors within 72 hours prior to dosing
- Lacks free access to water (inability to respond to thirst) or without ICU-level fluid monitoring and management
- Has a history or current diagnosis of nephrotic syndrome
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TolvaptanAlso: SAMSCATolvaptan 3.75-, 7.5-, 15-, and 30-mg Tablets. Dosage: Depending on age, weight and serum sodium response: Tablet (3.75 mg - 60 mg daily) Frequency: Once daily Duration: 30 (+2) days | Drug | Tolvaptan |
| PlaceboPlacebo tablet matching active drug | Other | Placebo |
Primary outcome
Change in serum sodium concentration
Time frame: Daily up to day 4
The average daily area under the curve (AUC) of change from baseline in serum sodium level up to Day 4 within the double-blind treatment period.
9 secondary outcomes
Change of average daily AUC from baseline at each visit in serum sodium level.
Time frame: Daily up to Day 30
Change from baseline in serum sodium concentration at Day 4.
Time frame: Day 4
Change from baseline in serum sodium concentration at Day 30.
Time frame: Daily up to Day 30
Percentage of subjects who require rescue therapy or fluid restriction at any time during the double-blind treatment period.
Time frame: Daily up to Day 30
Changes from baseline in ALT, AST and Total Bilirubin
Time frame: Daily up to Day 30
Clinically significant changes in vital signs.
Time frame: Daily up to Day 30
Incidence of dehydration AEs.
Time frame: Daily up to Day 30
Tanner staging progression score (at 30 days)
Time frame: Daily up to Day 30
Percentage of subjects with overly rapid correction in serum sodium ( ≥ 12 mmol/L in 24 hours).
Time frame: Daily up to Day 30
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2017.
Related trials for Hyponatremia
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Enrolling by invitationObservational study
International Multi-center Retrospective Study of Patients With Serum Sodium ≤110 mmol/L to Determine the Relationship Between Osmotic Demyelination Syndrome (ODS) and Rapid Correction of Hyponatremia
Hyponatremia Symptomatic, Osmotic Demyelination Syndrome
Active, not recruitingObservational study
Samsca Post-marketing General Drug Use-results Survey in Patients With Hyponatremia in SIADH
Antidiuretic Hormone, Inappropriate Secretion
Recruiting
Urea for Treatment of Hyponatremia in Patients With SIAD Unresponsive to Fluid Restriction
SIAD - Syndrome of Inappropriate Antidiuresis
Active, not recruitingObservational study
Hyponatremia - Complications, Prognosis, Epidemiology in Finnish Tertiary Care
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ann Dandurand, MD study director
Otsuka Pharmaceutical Development & Commercialization, Inc.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tolvaptan in people with Hyponatremia, run by Otsuka Pharmaceutical Development & Commercialization, Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 31 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in serum sodium concentration (time frame: Daily up to day 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2017.