Oseltamivir Treatment for Children Less Than 24 Months of Age With Influenza
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Influenza
Intervention: oseltamivir (Tamiflu®) (Drug)
Phase: Phase 1/Phase 2
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Summary
The purpose of this study is to learn how to treat influenza in children less than 2 years
of age. Tamiflu®, the drug being studied, is approved for treatment of children 1 year of
age and older with influenza. Researchers want to learn more about the activity of Tamiflu®
in the body to determine a dose of that is safe, well-tolerated, and effective in young
children with influenza. Children less than 24 months of age with confirmed influenza will
receive Tamiflu® 2 times a day for 5 days. Older participants will be enrolled first and
younger children will be enrolled after the safety data is reviewed for older participants.
Study procedures include blood samples, swabs from inside the nose, and body and nervous
system evaluations. Participants may be involved in study related procedures for up to 37
days.
Clinical Details
Official title: A Pharmacokinetic/Pharmacodynamic and Safety Evaluation of Oseltamivir (Tamiflu®) for the Treatment of Children Less Than 24 Months of Age With Confirmed Influenza Infection (CASG 114)
Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Oseltamivir Carboxylate AUC12 (Area Under the Curve).
Secondary outcome: Overall Reported Adverse Events (AEs) Thought to be Associated With Study Therapy.Number and Characteristics of Adverse Events (AEs) Described as Neurological Events. Incidence of Treatment Emergent AEs and Drug Related AEs by Cohort and Toxicity Grade Incidence of Treatment Emergent AEs and Drug Related AEs by Cohort Leading to Discontinuation of Study Medication Incidence of All Serious Adverse Events by Cohort and System Organ Class (SOC) Correlation of Clearance of Viral RNA by Culture With Pharmacokinetic Parameters by Cohort Correlation of Clearance of Viral RNA by Polymerase Chain Reaction (PCR) to Pharmacokinetic Parameters by Cohort.
Detailed description:
Oseltamivir is approved for prophylaxis and treatment of children 1 year of age and older
with influenza. Influenza treatments for children under the age of 1 year are needed because
mortality from influenza is high among this age group, even when there are no underlying
medical conditions. Oseltamivir is frequently used off-label in children less than 1 year of
age, with no data supporting the doses being used. Given the risk of severe or fatal
influenza infection in infants, the lack of repeat dose pharmacokinetic (PK) data in
children less than 2, the need for treatments in this population of children, and the fact
that oseltamivir is being used off-label in this population, the current study will
systematically study the PK and safety of oseltamivir in children less than 2 years of age
with confirmed influenza to determine the appropriate dose to be used in these age groups.
This data will be critical to pediatricians caring for these potentially gravely ill
infants. This study is a prospective, age-stratified PK/pharmacodynamic (PD) and safety
evaluation of oseltamivir therapy in children less than 24 months of age with confirmed
influenza infection. Participants will be stratified by age into the following enrollment
scheme at study initiation: 12-23 months (Cohort I), 9-11 months (Cohort II), 6-8 months
(Cohort III), 3-5 months (Cohort IV) and 0-2 months (Cohort V). At study onset, Cohort II
and III will be enrolled simultaneously. Cohorts IV and V will be enrolled sequentially by
decreasing age groups predicated upon the PK and safety data from the preceding cohort. In
the event of a public health emergency, the Data Safety Monitoring Board (DSMB) or Food and
Drug Administration (FDA) may authorize the following modifications to the proposed
enrollment plan: the opening of younger age cohorts without the full dataset from the next
higher age cohort, the re-opening of previously closed cohorts to obtain additional data
and/or the over-enrollment of any of the 5 cohorts. The oldest cohort (Cohort I) may be
enrolled at any time during the study. The primary study objective is to define the PK of
oseltamivir and oseltamivir carboxylate in children with confirmed influenza less than 2
years of age. The oseltamivir dose initially evaluated in Cohort I was the approved dose of
30 mg twice a day (bid). However, the oseltamivir carboxylate area under the curve (AUC)12
values for 5 of the 9 subjects enrolled in Cohort I as of August 5, 2009, were below the
lower range utilized for the other cohorts in the study, as was the GM AUC12 for Cohort I as
a group [(2589 nanograms per hour per milliliter (ngxh/mL)]. As a consequence, the DSMB
recommended on August 5, 2009, that the protocol be amended to utilize weight-based dosing
of oseltamivir in subjects subsequently enrolled in Cohort I, and to employ the targeted AUC
approach used for Cohorts II-V for this cohort as well. Based upon the PK data available as
of that date, the initial weight-based dose to be evaluated for Cohort I is 3. 5 mg/kg bid. A
dose of oseltamivir 3 mg/kg/dose orally bid for 5 days (10 doses) will be administered to
the first 9 subjects in each of Cohorts II-III. Additional subjects may be enrolled if the
target AUC12 range is not achieved. The proposed dose for subjects enrolled in Cohorts IV
and V will be 3 mg/kg/dose orally bid for 5 days (10 doses), although this dose may be
adjusted prior to opening Cohort IV or V based on the dose required to achieve the target
oseltamivir carboxylate AUC12 range in the previous cohort.
Eligibility
Minimum age: N/A.
Maximum age: 23 Months.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Signed informed consent from parent(s) or legal guardian(s).
- Age:
Cohort I: 12 - 23 mo. Cohort II: 9 - 11 mo. Cohort III: 6 - 8 mo. Cohort IV: 3 - 5 mo.
Cohort V: 0 - 2 mo.
- Confirmed laboratory diagnosis of influenza by viral culture or rapid influenza
diagnostic test within 96 hours prior to study enrollment.
- Duration of influenza symptoms less than or equal to 96 hours.
Exclusion Criteria:
- Concomitant vomiting illness that would preclude ability to take drug.
- Immunocompromised subject (e. g., malignancy, congenital agammaglobulinemia, HIV).
- Documented renal impairment (e. g., polycystic renal disease, nephrectomy, renal
transplantation, renal agenesis, dialysis requirement, renal failure, nephrotic
syndrome at any time prior to enrollment, current receipt of diuretic therapy).
- Documented hepatic impairment (e. g., congenital hepatitis, biliary atresia,
cholelithiasis).
- Gastrointestinal abnormality which might hinder absorption of an oral medication.
- Current receipt of inotropic drugs (e. g., epinephrine, norepinephrine, dopamine,
dobutamine).
- History of seizures.
- Documented congenital malformations of the central nervous system defined at birth
(e. g., hydranencephaly, prosencephaly, spina bifida).
Locations and Contacts
Centre Hospitalier de l'Universite Laval/ CHUQ, Quebec G1V 4G2, Canada
University of Alabama at Birmingham, Birmingham, Alabama 35117, United States
University of Alberta Hospital - Pediatrics, Edmonton, Alberta T6G 2B7, Canada
Arkansas Children's Hospital - Infectious Diseases, Little Rock, Arkansas 72202-3500, United States
Miller Children's Hospital Long Beach - Bickerstaff Family Center, Long Beach, California 90806-1701, United States
Children's Hospital of Orange County, Orange, California 92868-3835, United States
Rady Children's Hospital San Diego, San Diego, California 92123-4223, United States
Children's Hospital Colorado - Infectious Disease, Aurora, Colorado 80045-7106, United States
Children's National Medical Center - Sheikh Zayed Campus - Infectious Disease, Washington, District of Columbia 20010-2916, United States
University of Florida - Shands Children's Hospital, Gainesville, Florida 32610-0296, United States
University of South Florida - Tampa General Hospital - Pediatrics, Tampa, Florida 33606-3438, United States
Emory Children's Center - Pediatric Infectious Diseases, Atlanta, Georgia 30322-1014, United States
Emory University School of Medicine - Emory Children's Center - Pediatric Infectious Diseases, Atlanta, Georgia 30322, United States
Louisiana State University Health Shreveport - Pediatrics, Shreveport, Louisiana 71103-4228, United States
University of Mississippi - Children's Infectious Diseases, Jackson, Mississippi 39216-4505, United States
Washington University School of Medicine in St. Louis - Center for Clinical Studies, Saint Louis, Missouri 63110-1010, United States
University of Nebraska Medical Center - Children's Hospital and Medical Center - Infectious Diseases, Omaha, Nebraska 68114-4108, United States
Cohen Children's Medical Center - Pediatric Infectious Diseases, Manhasset, New York 11030-3816, United States
University of Rochester, Rochester, New York 14642, United States
SUNY Upstate Medical University Hospital - Pediatrics, Syracuse, New York 13210-2342, United States
Cincinnati Children's Hospital Medical Center - Infectious Diseases, Cincinnati, Ohio 45229-3026, United States
MetroHealth Medical Center - Pediatric Infectious Disease, Cleveland, Ohio 44109-1998, United States
The Hospital for Sick Children - Infectious Diseases, Toronto, Ontario M5G 1X8, Canada
Children's Hospital of Philadelphia - The Center for Pediatric Clinical Effectiveness, Philadelphia, Pennsylvania 19104-3309, United States
Children's Hospital of Pittsburgh of UPMC - General Academic Pediatric, Pittsburgh, Pennsylvania 15213-3205, United States
Rhode Island Hospital - Pediatrics, Providence, Rhode Island 02903-4923, United States
Vanderbilt University - Pediatric - Infectious Diseases, Nashville, Tennessee 37232-0011, United States
Parkland Memorial Hospital, Dallas, Texas 75235-7708, United States
The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9063, United States
Cook Children's Infectious Disease Services, Fort Worth, Texas 76104-2710, United States
University of Utah - Pediatric Pharmacology Program, Salt Lake City, Utah 84108-1457, United States
Seattle Children's Hospital - Infectious Diseases, Seattle, Washington 98105-3901, United States
Additional Information
Starting date: January 2007
Last updated: April 25, 2013
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