HyponatremiaPhase 3NCT02012959
Study of the Safety and Effectiveness of SAMSCA® (Tolvaptan) in Children and Adolescents With Euvolemic or Hypervolemic Hyponatremia
A Phase 3 study testing Tolvaptan in people with Hyponatremia, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 7 sites in 3 countries.
Trial summary
The purpose of this trial was to demonstrate that tolvaptan effectively and safely increases and maintains serum sodium concentrations in children and adolescent participants with euvolemic or hypervolemic hyponatremia. Read more about this study
- Who is it for?
- Ages 4 weeks to 17 years
- Conditions the study is for
- Hyponatremia
- What is being tested?
- Tolvaptan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 7 sitesin 3 countries
- Study dates
- 22 Sep 2015to 24 Jul 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 weeks to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Show all 27Show fewer
- 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
Trial locations and contacts
7 sites in 3 countries.
7 sites in 3 countries
United States5 sites
Study site
Aurora, Colorado, 80045
Study site
New York, New York, 10032
Study site
Richmond, Virginia, 23298-0270
Study site
Seattle, Washington, 98105
Study site
Washington D.C., District of Columbia, 20010
About this study
Official title: A Phase 3b, Multicenter, Open-label, Randomized Withdrawal Trial of the Effects of Titrated Oral SAMSCA ® (Tolvaptan) on Serum Sodium, Pharmacokinetics, and Safety in Children and Adolescent Subjects Hospitalized With Euvolemic or Hypervolemic Hyponatremia
The purpose of this trial was to demonstrate that tolvaptan effectively and safely increases and maintains serum sodium concentrations in children and adolescent participants with euvolemic or hypervolemic hyponatremia.
- Conditions
- Hyponatremia
- Being tested
- Tolvaptan
- Keywords
- Hyponatremia, Euvolemic, Hypervolemic, Serum sodium, Dilutional hyponatremia, Electrolyte abnormality, Electrolyte imbalance, Metabolic disease
- Medical subject headings
- Hyponatremia, Metabolic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TolvaptanDrug
Also called SAMSCA®
| Study group | Role | What they receive |
|---|---|---|
| Tolvaptan Early Withdrawal | Experimental | All participants initially received tolvaptan once daily for the first 2 days. A third day of treatment was permitted if a participant had not reached the desired sodium target improvement per the investigator's judgment.
At the end of Day 2 (or Day 3), responders (participants who achieved an increase in serum sodium by ≥4 millimoles/liter [mmol/L]) were randomized to either the Early or Late Withdrawal Group. Non-responders could continue treatment with tolvaptan for an additional 2 days.
Discontinued tolvaptan treatment immediately after randomization.
All participants were observed up to 14 days post randomization. Receives: Drug: Tolvaptan |
| Tolvaptan Late Withdrawal | Experimental | All participants initially received tolvaptan once daily for the first 2 days. A third day of treatment was permitted if a participant had not reached the desired sodium target improvement per the investigator's judgment.
At the end of Day 2 (or Day 3), responders (participants who achieved an increase in serum sodium by ≥4 mmol/L) were randomized to either the Early or Late Withdrawal Group in Treatment Phase B. Non-responders could continue treatment with tolvaptan for an additional 2 days.
Continued treatment for 2 additional days.
All participants were observed up to 14 days post randomization. Receives: Drug: Tolvaptan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change In Serum Sodium Concentration For Responders
Change in serum sodium concentration (mEq/L) for responders from Day 2 (or Day 2a) at the end of Treatment Phase A (where all participants received tolvaptan) to the end of Treatment Phase B for the Early compared to Late Withdrawal groups is reported. Once a participant was randomized to Treatment Phase B, any additional therapies for the purpose of raising serum sodium, including fluid restriction, were considered rescue therapy. Upon receipt of rescue therapy, a participant's endpoint data was collected and then censored from the efficacy analysis thereafter, unless specified.
Measured: Day 2/2a, Day 4
Secondary outcomes (2)
Change In Serum Sodium Concentration During Treatment Phase A
Change in serum sodium concentration (mEq/L) from baseline to the end of Day 2 (or 2a) during Treatment Phase A for all participants (responders and non-responders) is reported.
Measured: Baseline, Day 2/2a
Fluid Balance (Intake Minus Output) During Treatment Phase A
Every 6 hours and for the 24-hour daily interval on Days 1 and 2 during Treatment Phase A, fluid balance (milliliters [mL]) was determined by fluid intake (oral and intravenous) minus urine output. Improved fluid balance would be indicated through the induction of increased urine volume. Fluid balance was monitored per institutional guidelines.
Measured: Every 6 hours on Days 1 and 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2013 (estimated)
- Study start22 Sep 2015
- Primary completion24 Jul 2017
- Study completion24 Jul 2017
Why it stopped: Issues with participant recruitment \& enrollment which made the trial impossible or highly impracticable. Trial termination was not due to safety reasons.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Syneos Health
- Responsible party
- Sponsor
- Investigators
- Global Clinical Development, Study director, Otsuka Pharmaceutical Development & Commercialization, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02012959
- Sponsor's protocol ID
- 156-08-276
- Other IDs
- 2013-002005-59
- Status last verified
- Jul 2018
- First submitted
- 11 Dec 2013
- Last updated
- 26 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3b, Multicenter, Open-label, Randomized Withdrawal Trial of the Effects of Titrated Oral SAMSCA ® (Tolvaptan) on Serum Sodium, Pharmacokinetics, and Safety in Children and Adolescent Subjects Hospitalized With Euvolemic or Hypervolemic Hyponatremia
- ClinicalTrials.gov ID
- NCT02012959
- Acronym / sponsor ID
- 156-08-276
- Conditions
- Hyponatremia
- Keywords
- Hyponatremia, Euvolemic, Hypervolemic, Serum sodium, Dilutional hyponatremia, Electrolyte abnormality, Electrolyte imbalance, Metabolic disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Issues with participant recruitment \& enrollment which made the trial impossible or highly impracticable. Trial termination was not due to safety reasons.
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Syneos Health
- Study start
- 22 Sep 2015 (actual)
- Primary completion
- 24 Jul 2017 (actual)
- Study completion
- 24 Jul 2017 (actual)
- First posted
- 17 Dec 2013 (estimated)
- Results
- Posted 28 Aug 2018
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 was to demonstrate that tolvaptan effectively and safely increases and maintains serum sodium concentrations in children and adolescent participants with euvolemic or hypervolemic hyponatremia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tolvaptan Early Withdrawal | Experimental | Drug: TolvaptanAll participants initially received tolvaptan once daily for the first 2 days. A third day of treatment was permitted if a participant had not reached the desired sodium target improvement per the investigator's judgment. At the end of Day 2 (or Day 3), responders (participants who achieved an increase in serum sodium by ≥4 millimoles/liter [mmol/L]) were randomized to either the Early or Late Withdrawal Group. Non-responders could continue treatment with tolvaptan for an additional 2 days. Discontinued tolvaptan treatment immediately after randomization. All participants were observed up to 14 days post randomization. |
| Tolvaptan Late Withdrawal | Experimental | Drug: TolvaptanAll participants initially received tolvaptan once daily for the first 2 days. A third day of treatment was permitted if a participant had not reached the desired sodium target improvement per the investigator's judgment. At the end of Day 2 (or Day 3), responders (participants who achieved an increase in serum sodium by ≥4 mmol/L) were randomized to either the Early or Late Withdrawal Group in Treatment Phase B. Non-responders could continue treatment with tolvaptan for an additional 2 days. Continued treatment for 2 additional days. All participants were observed up to 14 days post randomization. |
Who may qualify
- Ages
- 4 weeks to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (27 listed)
- 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
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: SAMSCA® | Drug | Tolvaptan Early Withdrawal, Tolvaptan Late Withdrawal |
Primary outcome
Change In Serum Sodium Concentration For Responders
Time frame: Day 2/2a, Day 4
Change in serum sodium concentration (mEq/L) for responders from Day 2 (or Day 2a) at the end of Treatment Phase A (where all participants received tolvaptan) to the end of Treatment Phase B for the Early compared to Late Withdrawal groups is reported. Once a participant was randomized to Treatment Phase B, any additional therapies for the purpose of raising serum sodium, including fluid restriction, were considered rescue therapy. Upon receipt of rescue therapy, a participant's endpoint data was collected and then censored from the efficacy analysis thereafter, unless specified.
2 secondary outcomes
Change In Serum Sodium Concentration During Treatment Phase A
Time frame: Baseline, Day 2/2a
Fluid Balance (Intake Minus Output) During Treatment Phase A
Time frame: Every 6 hours on Days 1 and 2
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Global Clinical Development study director
Otsuka Pharmaceutical Development & Commercialization, Inc.
7 sites in 3 countries: see every site and its status.
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. at 7 sites in 3 countries.
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 8 inclusion and 27 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: stopped early, as of the sponsor's last update on 26 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Italy, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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?
Yes. Results are posted in the registry (first posted 28 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 For Responders (time frame: Day 2/2a, 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 26 Sep 2018.