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
研究概览
研究类型
注册 (实际的)
阶段
- 第三阶段
联系人和位置
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
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
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
实验性的: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. |
其他名称:
|
实验性的: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. |
其他名称:
|
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Change In Serum Sodium Concentration For Responders
大体时间: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.
|
Day 2/2a, Day 4
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Change In Serum Sodium Concentration During Treatment Phase A
大体时间:Baseline, Day 2/2a
|
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.
|
Baseline, Day 2/2a
|
Fluid Balance (Intake Minus Output) During Treatment Phase A
大体时间:Every 6 hours on Days 1 and 2
|
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.
|
Every 6 hours on Days 1 and 2
|
合作者和调查者
合作者
调查人员
- 研究主任:Global Clinical Development、Otsuka Pharmaceutical Development & Commercialization, Inc.
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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