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

PHRR121210-000032

Protocol No. 087-CL-096; FDA RSN No. 12K-991 and 12K-1302

Unspecified

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

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.

Start Date Duration in Months Target Completion Date Actual Completion Date
2012-02-01 48 2016-02-01 0000-00-00

Ongoing

Institution Classification Region LTO #
PPD Development (S) PTE. LTD. Private Business NCR
Institution Classification Region LTO #
Astellas Pharma Europe B.V. Private Business Netherlands
Institution Amount Region
Astellas Pharma Europe B.V. N/A Netherlands
Name E-Mail Phone Number Postal Address
Fridee-May Ortega Fridee-May.Ortega@ppdi.com +632 6896516 9/F Sun Life Centre 5th Avenue corner Rizal Drive, Bonifacio Global City, Taguig City
Name E-Mail Phone Number Postal Address
Astellas Pharma Global Development clintrials.info@us.astellas.com 800-888-7704 5473 Research & Development 3 Parkway North Deerfield, IL 60015, USA
Name Expertise Affiliation
Maria Rosario Cruz, MD Doctor Philippine Children's Medical Center
Project Location Institutional Ethics Review Board
Philippine Children's Medical Center Philippine Children's Medical Center IRB - Ethics Committee

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.

Mean change from baseline to Hour 48 in serum sodium as compared to placebo [ Time Frame: Baseline and Hour 48 ]

•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 ] •Number of patients with confirmed ≥ 4 mEq/L increase from baseline in serum sodium [ Time Frame: Hour 48 ] •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 ] •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 ] 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 ] Assessed by Urine Volume Collection •Change from baseline in free water clearance (FWC) every 12 hours [ Time Frame: Baseline, Hour 12, Hour 24, Hour 36, and Hour 48 ] Assessed by Urine Volume Collection •Incidence of adverse events including infusion site reactions [ Time Frame: Up to Day 9 ] •Incidence of serious adverse events (SAEs) [ Time Frame: Up to Day 32 ] •Safety assessed by vital signs, physical exams, neurological assessments, electrocardiograms (ECGs), and clinical laboratory measurements [ Time Frame: Up to Day 9 ] •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 ] 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 ] Based on conivaptan concentrations, the pharmacokinetics of the study population will be analyzed to determine median Vd

Recruiting

  • Brazil
  • India
  • Philippines
  • United States

Clinical Trial

Unspecified

Unspecified

None

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 and 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 participated in another clinical trial within past 30 days

Interventional

Conivaptan

Parallel assignment

Randomized

Double Blind (Subject, Caregiver, Investigator, Ou

Unspecified

Parallel

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.

Phase III

15

Unspecified

N/A

01 Feb 2012

Utilization Utilization Info
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