A Pharmacokinetic/Pharmacodynamic Study of Oseltamivir in Immunocompromised Children With Confirmed Influenza Infection

Hoffmann-La Roche20 enrolled

Overview

This open-label, randomized, adaptive, 2-arm, multicenter study will evaluate the pharmacokinetics and pharmacodynamics of oseltamivir (Tamiflu) in immunocompromised children, less than (\<) 13 years of age, with confirmed influenza infection. Participants will be randomized to receive either the standard dose or triple dose of oseltamivir orally daily for a minimum of 5 days and up to 20 days. Infants \<1 year of age will be randomized to the standard dose arm only.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Influenza

Interventions

OseltamivirDRUG

Participants will receive standard dose (30 to 75 milligrams \[mg\]) or triple standard dose (90 to 225 mg) of oseltamivir orally daily for up to maximum of 20 days. Standard dose of oseltamivir according to weight (except infants): 30 mg twice daily for \</= 15 kilograms (kg) body weight participants; 45 mg twice daily for 15 to 23 kg body weight participants; 60 mg twice daily for 23 to 40 kg body weight participants; and 75 mg twice daily for greater than (\>) 40 kg body weight participants. Standard dose for infants is 3 mg/kg.

Eligibility

Sex: ALLMax age: 12 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female children, \<13 years of age * Rapid influenza diagnostic test (RIDT), polymerase chain reaction (PCR), or viral culture positive for influenza * Immunocompromised * Symptoms/signs suggestive of influenza like illness (ILI) * Less than or equal to (\</=) 96 hours between onset of ILI and first dose of study drug Exclusion Criteria: * Clinical evidence of severe hepatic impairment * Infants with post-menstrual age (PMA) \<36 weeks * Clinical evidence of significant renal impairment * Allergy to oseltamivir or excipients * Hereditary fructose intolerance * Received anti-viral treatment with activity against influenza (for example amantadine, rimantadine, oseltamivir, laninamivir, peramivir, zanamivir, and ribavirin) or probenecid medication within 2 weeks prior to randomization

Locations (50)

Outcomes

Primary Outcomes

Steady State Area Under the Concentration-Time Curve From Time 0 to 12 Hours (AUC0-12) of Oseltamivir

Time frame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4

Steady State AUC0-12 of Oseltamivir Carboxylate

Time frame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4

Maximum Plasma Concentration (Cmax) of Oseltamivir

Time frame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4

Cmax of Oseltamivir Carboxylate

Time frame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4

Trough Plasma Concentration (Ctrough) of Oseltamivir

Time frame: Pre-dose (within 30 minutes prior to administration) on Days 3 or 4

Ctrough of Oseltamivir Carboxylate

Time frame: Pre-dose (within 30 minutes prior to administration) on Days 3 or 4

Time to Cessation of Viral Shedding, as Assessed by Polymerase Chain Reaction (PCR) or Culture Testing

Time frame: From randomization to negative PCR/culture test result (up to Day 50)

Secondary Outcomes

Time to Resolution of Influenza Symptoms (including fever),, as Assessed by Canadian Acute Respiratory Infections Scale (CARIFS)

Time frame: From randomization to resolution of all influenza symptoms (up to Day 50)

Number of Participants With Adverse Events

Data from ClinicalTrials.gov

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Lucile Packard Child Hosp; Pediatric Pulmonary Division

Palo Alto, California, United States

The Children's Hospital; Pediatric Infectious Diseases

Aurora, Colorado, United States

Tufts Medical Center

Boston, Massachusetts, United States

University of Minnesota

Minneapolis, Minnesota, United States

SUNY Upstate Medical University

Syracuse, New York, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Seattle Children's Hospital

Seattle, Washington, United States

UZ Brussel

Brussels, Belgium

Cliniques Universitaires St-Luc

Brussels, Belgium

UZ Leuven Gasthuisberg

Leuven, Belgium

...and 40 more locations

Time frame: Baseline up to Day 50

Number of Participants With Influenza Associated Complications

Time frame: Baseline up to Day 50

Number of Participants With Viral Resistance

Time frame: Baseline up to Day 50

Half-life (t1/2) of Oseltamivir

Time frame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4

t1/2 of Oseltamivir Carboxylate

Time frame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4

Time to Maximum Concentration (Tmax) of Oseltamivir

Time frame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4

Tmax of Oseltamivir Carboxylate

Time frame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4

Elimination Rate Constant (Ke) of Oseltamivir

Time frame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4

Ke of Oseltamivir Carboxylate

Time frame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4

Apparent Volume of Distribution (V/F) of Oseltamivir

Time frame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4

V/F of Oseltamivir Carboxylate

Time frame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4

Apparent Clearance (CL/F) of Oseltamivir

Time frame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4

CL/F of Oseltamivir Carboxylate

Time frame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4

Time to Last Measurable Concentration (Tlast) of Oseltamivir

Time frame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4

Tlast of Oseltamivir Carboxylate

Time frame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4

Last Measurable Concentration (Clast) of Oseltamivir

Time frame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4

Clast of Oseltamivir Carboxylate

Time frame: Pre-dose (within 30 minutes prior to administration), 1.5, 4, 8 hours post-dose on Days 3 or 4