Clinical trial NCT01451411: A Study to Assess the Efficacy, Safety and Pharmacokinetics of Intravenous Conivaptan (Vaprisol®) in Pediatric Subjects With Euvolemic or Hypervolemic Hyponatremia
Official title: 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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hyponatremia
Keywords: Serum Sodium
Euvolemia
Hypervolemia
Vaprisol®
Conivaptan
YM087
Lead sponsor: Cumberland Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2011-10-13
Enrollment: 4
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to evaluate the efficacy, safety and pharmacokinetics of intravenous conivaptan in pediatric subjects with abnormally low concentration of sodium in blood.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Change From Baseline to the End of the 48-hour Treatment Period in Serum Sodium
timeFrame: baseline and 48 hours
Secondary outcomes:
measure: Time From the First Dose of Study Medication to a Confirmed ≥ 4 mEq/L Increase From Baseline in Serum Sodium
timeFrame: 48 hours
measure: Number of Patients With Confirmed ≥ 4 mEq/L Increase From Baseline in Serum Sodium
timeFrame: baseline and 48 hours
measure: 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)
timeFrame: baseline and 48 hours
measure: Change From Baseline in Effective Water Clearance (EWC) Every 12 Hours
timeFrame: Baseline, Hours 12, 24, 36 and 48
measure: Change From Baseline in Free Water Clearance (FWC)
timeFrame: Baseline and 48 hours
measure: Number of Participants With an Overly Rapid Rise in Serum Sodium From Baseline
timeFrame: baseline and Hours 3, 8, 12 and 24.
measure: Population Pharmacokinetics: Clearance (CL)
timeFrame: Up to Hour 60
measure: Population Pharmacokinetics: Volume of Distribution (Vd)
timeFrame: Up to Hour 60
Other outcomes:
Locations:
city: New York
country: United States
facility: Children's Hospital of New York - Presbyterian
state: New York
city: Bogota
country: Colombia
facility: Fundación Cardioinfantil - Instituto Cardiológico
city: Cali, Valle
country: Colombia
facility: Fundación Valle del Lili
Study officials:
affiliation: Cumberland Pharmaceuticals, Inc.
name: Art Wheeler, MD
role: STUDY_DIRECTOR
References: