A Study to Assess the Efficacy, Safety and Pharmacokinetics of Intravenous Conivaptan (Vaprisol®) in Pediatric Subjects With Euvolemic or Hypervolemic Hyponatremia

This study has suspended participant recruitment.
Sponsor:
Information provided by (Responsible Party):
Cumberland Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01451411
First received: October 5, 2011
Last updated: April 30, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Hyponatremia
Drug: Conivaptan hydrochloride
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Cumberland Pharmaceuticals:

Primary Outcome Measures:
  • Mean change from baseline to Hour 48 in serum sodium as compared to placebo [ Time Frame: Baseline and Hour 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time from the first dose of study medication to a confirmed ≥ 4 mEq/L increase from baseline in serum sodium [ Time Frame: Baseline and Hour 48 ] [ Designated as safety issue: No ]
  • Number of patients with confirmed ≥ 4 mEq/L increase from baseline in serum sodium [ Time Frame: Hour 48 ] [ Designated as safety issue: No ]
  • Change from baseline in serum sodium at each time point [ Time Frame: Baseline, Hour 0, Hour 3, Hour 8, Hour 12, Hour 24, Hour 32, Hour 40 and Hour 48 ] [ Designated as safety issue: No ]
  • Number of subjects with confirmed > 6 mEq/L increase from baseline in serum sodium or a confirmed normal serum sodium level [ Time Frame: Hour 48 ] [ Designated as safety issue: No ]
    Normal serum sodium level defined as at least 135 mEq/L

  • Change from baseline in effective water clearance (EWC) every 12 hours [ Time Frame: Baseline, Hour 12, Hour 24, Hour 36, and Hour 48 ] [ Designated as safety issue: No ]
    Assessed by Urine Volume Collection

  • Change from baseline in free water clearance (FWC) [ Time Frame: Baseline and Hour 48 ] [ Designated as safety issue: No ]
    Assessed by Urine Volume Collection

  • Incidence of adverse events including infusion site reactions [ Time Frame: Up to Day 9 ] [ Designated as safety issue: No ]
  • Incidence of serious adverse events (SAEs) [ Time Frame: Up to Day 32 ] [ Designated as safety issue: No ]
  • Safety assessed by vital signs, physical exams, neurological assessments, electrocardiograms (ECGs), and clinical laboratory measurements [ Time Frame: Up to Day 9 ] [ Designated as safety issue: No ]
  • Overly rapid rise in serum sodium from baseline [ Time Frame: Baseline and Hour 24 ] [ Designated as safety issue: No ]
    Overly rapid rise in serum sodium is defined as an absolute serum sodium of 145 mEq/L or an increase in serum sodium of greater than 12 mEq/L

  • Population Pharmacokinetics: Clearance (CL) [ Time Frame: Up to Hour 60 ] [ Designated as safety issue: No ]
    Based on conivaptan concentrations, the pharmacokinetics of the study population will be analyzed to determine median CL

  • Population Pharmacokinetics: Volume of distribution (Vd) [ Time Frame: Up to Hour 60 ] [ Designated as safety issue: No ]
    Based on conivaptan concentrations, the pharmacokinetics of the study population will be analyzed to determine median Vd


Estimated Enrollment: 80
Study Start Date: February 2012
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Conivaptan hydrochloride Drug: Conivaptan hydrochloride
Intravenous
Other Names:
  • Vaprisol®
  • YM087
Placebo Comparator: Placebo Drug: Placebo
Intravenous

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

Ages Eligible for Study:   2 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01451411

Locations
United States, Arkansas
Arkansas Children's Hospital Research Institute
Little Rock, Arkansas, United States, 72202
United States, Indiana
Riley Children's Hospital
Indianapolis, Indiana, United States, 46202
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536-0298
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Children's Hospital of New York - Presbyterian
New York, New York, United States, 10032
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Colombia
Fundación Cardioinfantil - Instituto Cardiológico
Bogota, Colombia
Fundación Valle del Lili
Cali, Valle, Colombia
Sponsors and Collaborators
Cumberland Pharmaceuticals
Investigators
Study Director: Art Wheeler, MD Cumberland Pharmaceuticals Inc.
  More Information

No publications provided

Responsible Party: Cumberland Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01451411     History of Changes
Other Study ID Numbers: 087-CL-096
Study First Received: October 5, 2011
Last Updated: April 30, 2014
Health Authority: United States: Food and Drug Administration
Mexico: Federal Commission for Sanitary Risks Protection
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
Brazil: Ministry of Health
Colombia: National Institutes of Health
Peru: Instituto Nacional de Salud
Philippines : Food and Drug Administration

Keywords provided by Cumberland Pharmaceuticals:
Serum Sodium
Euvolemia
Hypervolemia
Vaprisol®
Conivaptan
YM087

Additional relevant MeSH terms:
Hyponatremia
Metabolic Diseases
Water-Electrolyte Imbalance

ClinicalTrials.gov processed this record on October 23, 2014