- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01451411
A Study to Assess the Efficacy, Safety and Pharmacokinetics of Intravenous Conivaptan (Vaprisol®) in Pediatric Subjects With Euvolemic or Hypervolemic Hyponatremia
A Phase III, Double-Blind, Randomized, Placebo-Controlled, Multi-Center, Dose-Titration Study to Assess the Efficacy, Safety and Pharmacokinetics of Intravenous Conivaptan (Vaprisol®) in Pediatric Subjects With Euvolemic or Hypervolemic Hyponatremia
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
A 3:1 randomization between conivaptan and placebo will be implemented and randomization will be further stratified in a 1:1:2 ratio for age groups: 2-5 years, 6-10 years, and 11-17 years.
Subjects will need to remain hospitalized for the 48-hour Treatment Period through Hour 96 (Day 4). There will be a follow-up safety visit on Day 9 or day of hospital discharge, whichever occurs first. There is a final follow-up phone call at Day 32 to assess if any serious adverse events have occurred since hospital discharge.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Bogota, Colombia
- Fundación Cardioinfantil - Instituto Cardiológico
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Cali, Valle, Colombia
- Fundacion Valle del Lili
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New York
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New York, New York, United States, 10032
- Children's Hospital of New York - Presbyterian
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Subject is euvolemic or hypervolemic hyponatremia upon clinical presentation
- Subject has serum sodium value ≥ 115 mEq/L (115 mmol/L) and < 130 mEq/L (130 mmol/L) during the 24 hours preceding inclusion into the study
- Female subject of childbearing potential must have a negative serum pregnancy test and must be premenarchal, surgically sterile or must practice a method of birth control
Exclusion Criteria:
- Female subject is pregnant or lactating
- Subject has a body mass index (BMI) < the 3rd percentile or > the 97th percentile for their age and stature according to the World Health Organization; Body mass index-for-age percentiles charts for boys and girls ages 2 to 20
- Subject has clinical evidence of volume depletion, dehydration or hypovolemia
- Subject with hypovolemic hyponatremia or transient causes of hyponatremia that are likely to resolve during the time of study participation
- Subjects with a cause of hyponatremia that is most appropriately corrected by alternative therapies
- Subject is expected to receive emergent treatment for hyponatremia during the treatment period of the study
- Subject has clinical evidence of hypotension
- Subject has uncontrolled hypertension > the 99th percentile for their age
- Subject has uncontrolled bradyarrhythmias or tachyarrhythmias requiring emergent pacemaker placement or treatment
- Subject has untreated severe hypothyroidism, hyperthyroidism or adrenal insufficiency
- Subject has known urinary outflow obstruction, unless subject is, or can be catheterized during the study
- Subject has estimated creatinine clearance < 30 mL/min during the seven days prior to study drug administration
- Subject has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations > 3 times the upper limit of normal reference range during the seven days prior to study drug administration
- Subject has serum albumin ≤ 1.5 g/dL during the seven days prior to study drug administration
- Subject has white blood cell count (WBC) < 3000/micro-liter documented any time during seven days prior to study drug administration or anticipated drop in WBC to < 3000/micro-liter during the period of the study due to chemotherapy
- Subject currently has unstable hepatic function or a history of hepatic encephalopathy, or bleeding esophageal varices within the last 3 months
- Subject has acute heart failure. Prior history of heart failure is allowed if there are no current signs/symptoms
- Subject has a non-fasting blood glucose value ≥ 275 mg/dL
- Subject requires or is suspected to require treatment with potent inhibitors or potent inducers of CYP3A4
- Subject was administered hypertonic saline or oral salt supplement within 24 hours prior to study drug administration
- Subject requires the use of medications used in the treatment of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH): including lithium salts, urea or demeclocycline during the week prior to screening and throughout the study drug treatment period
- Subject has any condition that may interfere with treatment or evaluation of safety
- Subject has received investigational therapy (including placebo) within 28 days or 5 half lives, whichever is longer
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Placebo Comparator: Placebo
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Intravenous
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Experimental: Conivaptan hydrochloride
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Intravenous
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Mean Change From Baseline to the End of the 48-hour Treatment Period in Serum Sodium
Time Frame: baseline and 48 hours
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baseline and 48 hours
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time From the First Dose of Study Medication to a Confirmed ≥ 4 mEq/L Increase From Baseline in Serum Sodium
Time Frame: 48 hours
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48 hours
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Number of Patients With Confirmed ≥ 4 mEq/L Increase From Baseline in Serum Sodium
Time Frame: baseline and 48 hours
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baseline and 48 hours
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Number of Subjects With Confirmed > 6 mEq/L Increase From Baseline in Serum Sodium or a Confirmed Normal Serum Sodium Level (Greater Than or Equal to 135 mEq/L)
Time Frame: baseline and 48 hours
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baseline and 48 hours
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Change From Baseline in Effective Water Clearance (EWC) Every 12 Hours
Time Frame: Baseline, Hours 12, 24, 36 and 48
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Baseline, Hours 12, 24, 36 and 48
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Change From Baseline in Free Water Clearance (FWC)
Time Frame: Baseline and 48 hours
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Baseline and 48 hours
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Number of Participants With an Overly Rapid Rise in Serum Sodium From Baseline
Time Frame: baseline and Hours 3, 8, 12 and 24.
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an absolute serum sodium of 145 mEq/L at Hour 24 or an increase in serum sodium of greater than 12 mEq/L
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baseline and Hours 3, 8, 12 and 24.
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Population Pharmacokinetics: Clearance (CL)
Time Frame: Up to Hour 60
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Based on conivaptan concentrations, the pharmacokinetics of the study population will be analyzed to determine median CL
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Up to Hour 60
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Population Pharmacokinetics: Volume of Distribution (Vd)
Time Frame: Up to Hour 60
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Based on conivaptan concentrations, the pharmacokinetics of the study population will be analyzed to determine median Vd
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Up to Hour 60
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Art Wheeler, MD, Cumberland Pharmaceuticals, Inc.
Study record dates
Study Major Dates
Study Start
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 (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 087-CL-096
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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