Pharmacokinetic/Pharmacodynamic and Safety Evaluation of Intravenous Peramivir in Children With Influenza

November 10, 2011 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

A Pharmacokinetic/Pharmacodynamic and Safety Evaluation of Investigational Intravenous Peramivir in Children With Influenza Disease (CASG 117)

The purposes of this study are to evaluate the pharmacokinetics (affect the body has on a drug), and pharmacodynamics (affect the drug has on the body) and safety of an experimental intravenous (within a vein) flu medication, peramivir, in children. Participants will include 63 hospitalized children with confirmed flu. Children will be grouped according to age and younger children will not receive drug until safety data from the groups of older children are reviewed. Hospitalized children may receive up to 5 doses of peramivir. Study procedures include: nasal/throat swabs, reporting any experienced side effects, physical examination including assessment of the nervous system, and blood sample collection. Participants will be involved in study related procedures for up to 28 days.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Infants and young children are at greatest risk of mortality from epidemic influenza. Influenza medications currently approved for use in the United States are administered orally or via inhalation. Availability of a parenteral influenza medication could be of great importance in medical and public health responses to both seasonal and pandemic influenza. Peramivir is an experimental parenteral influenza drug that is in advanced stages of clinical development. The primary objective of this study is to define the pharmacokinetics (PK) of peramivir in children with confirmed influenza. The secondary objectives are to: assess the safety and tolerability of intravenous (IV) peramivir in children with influenza; assess viral dynamics as a function of drug PK; and assess virus susceptibility to peramivir. This study is a prospective, open-label, age-stratified PK/pharmacodynamic (PD) and safety evaluation of investigational IV peramivir in hospitalized children with influenza infection who are unable to receive or have failed at least three days oseltamivir or zanamivir therapy. A minimum of 63 children with confirmed influenza will be enrolled into 1 of 7 age cohorts: Cohort I (>= 12 years to < 18 years); Cohort II (>= 6 years to < 12 years); Cohort III (>= 2 years to < 6 years); Cohort IV (>= 181 days to < 2 years); Cohort V (>= 91 days to < 181 days); Cohort VI (>= 31 days to < 91 days) and Cohort VII (Birth to < 31 days). Only hospitalized children will be enrolled. At study onset, Cohorts I, II and III (children from >=2 years to < 18 years of age) will be enrolled initially. When PK and safety data from 9 total subjects enrolled Cohort I, Cohort II and/or Cohort IIII are available and reviewed by the study's Data and Safety Monitoring Board (DSMB), Cohorts IV-VII will be opened for enrollment. The initial doses selected for use were based on modeling and from a recently completed clinical trial study of a fixed dose (10 mg/kg) of peramivir in pediatric patients with influenza. In the current study, PK data will be obtained in a real time basis, and doses in each cohort may be modified if the target exposure [area under the curve (AUC) 24] falls outside of a pre-specified range. Additional enrollments may be allowed if the dose requires modification in a given cohort. In the event of a public health emergency, the National Institutes of Health (NIH), DSMB, or Food and Drug Administration (FDA) may that all cohorts be open for enrollment. Subjects will receive IV Peramivir once daily for 5 days or until the day of hospital discharge, whichever comes first, and PK blood draws will be obtained around the second dose. In addition to PK and PD, this study will carefully assess clinical disease course and adverse events (AEs), including neurologic AEs. Safety evaluations also will include neurologic assessments, general physical assessments, and AE and serious adverse event (SAE) reporting. Sequential nasopharyngeal specimens will be obtained for virologic assessments, including viral cultures, polymerase chain reaction (PCR) for viral ribonucleic acid (RNA) (quantitative), and analysis of antiviral resistance.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham
    • Arkansas
      • Little Rock, Arkansas, United States, 72202-3591
        • Arkansas Children's Hospital
    • California
      • Orange, California, United States, 92868
        • Children's Hospital of Orange County
      • Stanford, California, United States, 94306
        • Stanford University
    • Colorado
      • Denver, Colorado, United States, 80218
        • The Children's Hospital - Denver, Colorado
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Childrens National Medical Center
    • Florida
      • Tampa, Florida, United States, 33606
        • University of South Florida
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • University Of Louisville
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane University
      • Shreveport, Louisiana, United States, 71103
        • Louisiana State University
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston Medical Center
      • Worcester, Massachusetts, United States, 01655
        • University of Massachusetts
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University in St. Louis
    • Nebraska
      • Omaha, Nebraska, United States, 68198-5400
        • University of Nebraska Medical Center
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • The Children's Hospital at Saint Peter's University Hospital
    • New York
      • Manhasset, New York, United States, 11030
        • North Shore-Long Island Jewish Health System
      • New York, New York, United States, 10016
        • NYU School of Medicine
      • New York, New York, United States, 10065
        • New York Presbyterian Hospital-Weill Medical College of Cornell University
      • Rochester, New York, United States, 14642
        • University of Rochester
      • Stony Brook, New York, United States, 11794-8111
        • SUNY at Stony Brook
      • Syracuse, New York, United States, 13210
        • SUNY Upstate Medical University
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Carolinas Medical Center
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Ohio
      • Cleveland, Ohio, United States, 44109
        • MetroHealth Medical Center
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital
    • Tennessee
      • Nashville, Tennessee, United States, 37232-2581
        • Vanderbilt University
    • Texas
      • Dallas, Texas, United States, 75235
        • The University of Texas Southwestern Medical Center at Dallas
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria: -Signed informed consent from parent(s) or legal guardian(s), and signed informed assent as age appropriate. -Age: Cohort I:>/= 12 years to < 18 years. Cohort II: >/= 6 years to < 12 years. Cohort III: >/= 2 years to < 6 years. Cohort IV: >/= 181 days to < 2 years. Cohort V: >/= 91 days to < 181 days. Cohort VI: >/= 31 days to < 91 days. Cohort VII: Birth to < 31 days -Confirmed laboratory diagnosis of influenza by viral culture, polymerase chain reaction (PCR), or rapid influenza diagnostic test. -Hospitalized with influenza or complications of influenza -Subject cannot tolerate oral or inhaled influenza antiviral therapy, or has not responded to at least 3 days of oral or inhaled influenza antiviral therapy, as determined by the physician. -Females of childbearing potential must have one of the following: a. Subject has been sexually abstinent for the 4 weeks prior to date of screening evaluation and is willing to remain abstinent through 4 weeks after study drug administration b. Subject has been using oral contraceptives or other form of hormonal birth control for 3 months prior to the study and will continue to use through 4 weeks after study-drug discontinuation c. Subject has been using an intra-uterine device, or adequate double-barrier method (such as condom or diaphragm with spermicide) as birth control for 4 weeks prior to date of screening and will continue use through 4 weeks after study drug administration d. Subject is surgically sterile (e.g., hysterectomy, tubal ligation) -Sexually active males must ensure that their female partners of childbearing potential will utilize approved contraceptive methods to avoid pregnancy Exclusion Criteria: -Currently receiving peritoneal dialysis. -Currently requiring extracorporeal membrane oxygenation (ECMO). -Imminent demise. -Documented H275Y mutation (note: it is unlikely that resistance testing will have been completed for most subjects). -New onset seizure disorder with this acute illness. -Suspicion of significant renal impairment (e.g., polycystic renal disease, nephrectomy, renal transplantation within the past 6 months, renal agenesis, chronic renal failure, anuria). -Pregnancy (positive urine or serum pregnancy test at screening evaluation for females of childbearing potential). -Females who are breastfeeding. -Inability to comply with protocol-required procedures. -Presence of any pre-existing condition that, in the opinion of the investigator, would place the subject at an unreasonable increased risk through participation in this study. -Alternate explanation for clinical findings, as determined by the investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort I
Cohort I: >/= 12 years to < 18 years. Peramivir administered daily for five days or until the day of hospital discharge, whichever comes first.
Drug: Peramivir
Peramivir is a liquid for parenteral administration. Cohort I: Peramivir, 10 mg/kg intravenously (IV) every day (QD) (maximum of 600 mg/day) for 5 days or until hospital discharge, whichever comes first. Cohort II: Peramivir 12 mg/kg IV QD (maximum of 600 mg/day) for 5 days or until hospital discharge, whichever comes first. Cohort III: Peramivir 16 mg/kg QD (maximum of 600 mg/day) for 5 days or until hospital discharge, whichever comes first. Proposed doses for subjects in Cohorts IV, V, VI, and VII are 18, 18, 14 and 12 mg/kg, respectively, IV, QD for 5 days or until hospital discharge, whichever comes first. IV peramivir will be administered over 60 minutes.
Experimental: Cohort II
Cohort II: >/= 6 years to < 12 years
Drug: Peramivir
Peramivir is a liquid for parenteral administration. Cohort I: Peramivir, 10 mg/kg intravenously (IV) every day (QD) (maximum of 600 mg/day) for 5 days or until hospital discharge, whichever comes first. Cohort II: Peramivir 12 mg/kg IV QD (maximum of 600 mg/day) for 5 days or until hospital discharge, whichever comes first. Cohort III: Peramivir 16 mg/kg QD (maximum of 600 mg/day) for 5 days or until hospital discharge, whichever comes first. Proposed doses for subjects in Cohorts IV, V, VI, and VII are 18, 18, 14 and 12 mg/kg, respectively, IV, QD for 5 days or until hospital discharge, whichever comes first. IV peramivir will be administered over 60 minutes.
Experimental: Cohort III
Cohort III: >/= 2 years to < 6 years
Drug: Peramivir
Peramivir is a liquid for parenteral administration. Cohort I: Peramivir, 10 mg/kg intravenously (IV) every day (QD) (maximum of 600 mg/day) for 5 days or until hospital discharge, whichever comes first. Cohort II: Peramivir 12 mg/kg IV QD (maximum of 600 mg/day) for 5 days or until hospital discharge, whichever comes first. Cohort III: Peramivir 16 mg/kg QD (maximum of 600 mg/day) for 5 days or until hospital discharge, whichever comes first. Proposed doses for subjects in Cohorts IV, V, VI, and VII are 18, 18, 14 and 12 mg/kg, respectively, IV, QD for 5 days or until hospital discharge, whichever comes first. IV peramivir will be administered over 60 minutes.
Experimental: Cohort V
Cohort V: >/= 91 days to < 181 days
Drug: Peramivir
Peramivir is a liquid for parenteral administration. Cohort I: Peramivir, 10 mg/kg intravenously (IV) every day (QD) (maximum of 600 mg/day) for 5 days or until hospital discharge, whichever comes first. Cohort II: Peramivir 12 mg/kg IV QD (maximum of 600 mg/day) for 5 days or until hospital discharge, whichever comes first. Cohort III: Peramivir 16 mg/kg QD (maximum of 600 mg/day) for 5 days or until hospital discharge, whichever comes first. Proposed doses for subjects in Cohorts IV, V, VI, and VII are 18, 18, 14 and 12 mg/kg, respectively, IV, QD for 5 days or until hospital discharge, whichever comes first. IV peramivir will be administered over 60 minutes.
Experimental: Cohort VII
Cohort VII: birth to < 31 days
Drug: Peramivir
Peramivir is a liquid for parenteral administration. Cohort I: Peramivir, 10 mg/kg intravenously (IV) every day (QD) (maximum of 600 mg/day) for 5 days or until hospital discharge, whichever comes first. Cohort II: Peramivir 12 mg/kg IV QD (maximum of 600 mg/day) for 5 days or until hospital discharge, whichever comes first. Cohort III: Peramivir 16 mg/kg QD (maximum of 600 mg/day) for 5 days or until hospital discharge, whichever comes first. Proposed doses for subjects in Cohorts IV, V, VI, and VII are 18, 18, 14 and 12 mg/kg, respectively, IV, QD for 5 days or until hospital discharge, whichever comes first. IV peramivir will be administered over 60 minutes.
Experimental: Cohort VI
Cohort VI: >/= 31 days to < 91 days
Drug: Peramivir
Peramivir is a liquid for parenteral administration. Cohort I: Peramivir, 10 mg/kg intravenously (IV) every day (QD) (maximum of 600 mg/day) for 5 days or until hospital discharge, whichever comes first. Cohort II: Peramivir 12 mg/kg IV QD (maximum of 600 mg/day) for 5 days or until hospital discharge, whichever comes first. Cohort III: Peramivir 16 mg/kg QD (maximum of 600 mg/day) for 5 days or until hospital discharge, whichever comes first. Proposed doses for subjects in Cohorts IV, V, VI, and VII are 18, 18, 14 and 12 mg/kg, respectively, IV, QD for 5 days or until hospital discharge, whichever comes first. IV peramivir will be administered over 60 minutes.
Experimental: Cohort IV
Cohort IV: >/= 181 days to < 2 years
Drug: Peramivir
Peramivir is a liquid for parenteral administration. Cohort I: Peramivir, 10 mg/kg intravenously (IV) every day (QD) (maximum of 600 mg/day) for 5 days or until hospital discharge, whichever comes first. Cohort II: Peramivir 12 mg/kg IV QD (maximum of 600 mg/day) for 5 days or until hospital discharge, whichever comes first. Cohort III: Peramivir 16 mg/kg QD (maximum of 600 mg/day) for 5 days or until hospital discharge, whichever comes first. Proposed doses for subjects in Cohorts IV, V, VI, and VII are 18, 18, 14 and 12 mg/kg, respectively, IV, QD for 5 days or until hospital discharge, whichever comes first. IV peramivir will be administered over 60 minutes.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Peramivir dose that provides area under the curve (AUC)24 between 60 microgram (mcg) hour(hr)/liter (L) and 94 mcg hr/L.
Time Frame: Within 15 minutes prior to dosing, and at the following timepoints measured from the time of the start of the infusion: 1-1.25 hours (end of infusion), 2-3 hours, 5-7 hours, 10-12 hours, and 22-24 hours post-dosing.
Within 15 minutes prior to dosing, and at the following timepoints measured from the time of the start of the infusion: 1-1.25 hours (end of infusion), 2-3 hours, 5-7 hours, 10-12 hours, and 22-24 hours post-dosing.
Pharmacokinetic parameters for peramivir, including AUC24, maximum serum concentration (Cmax), half-life (T1/2), Clearance (CL), and time to maximum concentration (Tmax).
Time Frame: Within 15 minutes prior to dosing, and at the following timepoints measured from the time of the start of the infusion: 1-1.25 hours (end of infusion), 2-3 hours, 5-7 hours, 10-12 hours, and 22-24 hours post-dosing.
Within 15 minutes prior to dosing, and at the following timepoints measured from the time of the start of the infusion: 1-1.25 hours (end of infusion), 2-3 hours, 5-7 hours, 10-12 hours, and 22-24 hours post-dosing.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Safety: overall incidence of adverse events.
Time Frame: Day 1 to Day 28
Day 1 to Day 28
Safety: the incidence of grade 3-4 adverse events or severe adverse events.
Time Frame: Day 1 to Day 28
Day 1 to Day 28
Safety: the incidence of adverse events considered to be related to study treatment.
Time Frame: Day 1 to Day 28
Day 1 to Day 28
Safety: the incidence of adverse events leading to discontinuation of study drug.
Time Frame: Day 1 to Day 28
Day 1 to Day 28
Virologic: proportion of subjects who are negative for viral ribonucleic acid (RNA) by reverse transcriptase-polymerase chain reaction (PCR).
Time Frame: Day 3, 5, and 10.
Day 3, 5, and 10.
Virologic: incidence of treatment emergent peramivir resistant virus.
Time Frame: Study days 1, 3, 5, and 10.
Study days 1, 3, 5, and 10.
Virologic: time to no detectable viral ribonucleic acid (RNA) by polymerase chain reaction (PCR).
Time Frame: Study days 1, 3, 5, and 10.
Study days 1, 3, 5, and 10.
Virologic: quantitative viral load over time.
Time Frame: Study days 1, 3, 5, and 10.
Study days 1, 3, 5, and 10.
Safety: the incidence of severe or grade 3 and 4 treatment related adverse events.
Time Frame: Day 1 to Day 28
Day 1 to Day 28
Safety: the incidence of treatment-related serious adverse events.
Time Frame: Day 1 to Day 28
Day 1 to Day 28
Safety: the incidence of serious adverse events and deaths.
Time Frame: Day 1 to Day 28
Day 1 to Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Institute of Allergy and Infectious Diseases (NIAID)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2011

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 4, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 4, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 5, 2010

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 11, 2011

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 10, 2011

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 09-0064
  • N01AI30025C
  • BCX1812-205, CASG 117

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.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings