- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02012959
Study of the Safety and Effectiveness of SAMSCA® (Tolvaptan) in Children and Adolescents With Euvolemic or Hypervolemic Hyponatremia
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
Study Overview
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Rome, Italy, 00165
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London, United Kingdom, WC1N 3JH
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Colorado
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Aurora, Colorado, United States, 80045
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District of Columbia
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Washington, District of Columbia, United States, 20010
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New York
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New York, New York, United States, 10032
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Virginia
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Richmond, Virginia, United States, 23298-0270
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Washington
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Seattle, Washington, United States, 98105
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Tolvaptan Early Withdrawal
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. |
Other Names:
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Experimental: Tolvaptan Late Withdrawal
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. |
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change In Serum Sodium Concentration For Responders
Time Frame: Day 2/2a, Day 4
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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.
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Day 2/2a, Day 4
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change In Serum Sodium Concentration During Treatment Phase A
Time Frame: Baseline, Day 2/2a
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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.
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Baseline, Day 2/2a
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Fluid Balance (Intake Minus Output) During Treatment Phase A
Time Frame: Every 6 hours on Days 1 and 2
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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.
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Every 6 hours on Days 1 and 2
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Collaborators and Investigators
Collaborators
Investigators
- Study Director: Global Clinical Development, Otsuka Pharmaceutical Development & Commercialization, Inc.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 156-08-276
- 2013-002005-59 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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