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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01715909
First received: October 25, 2012
Last updated: September 14, 2016
Last verified: September 2016
  Purpose
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.

Condition Intervention Phase
Influenza
Drug: Oseltamivir
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    The AUC (0-12) results will be extrapolated using the pharmacokinetic model from the available data collected during the study.

  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Trough Plasma Concentration (Ctrough) of Oseltamivir [ Time Frame: Pre-dose (within 30 minutes prior to administration) on Days 3 or 4 ] [ Designated as safety issue: No ]
  • Ctrough of Oseltamivir Carboxylate [ Time Frame: Pre-dose (within 30 minutes prior to administration) on Days 3 or 4 ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
  • Number of Participants With Adverse Events [ Time Frame: Baseline up to Day 50 ] [ Designated as safety issue: No ]
  • Number of Participants With Influenza Associated Complications [ Time Frame: Baseline up to Day 50 ] [ Designated as safety issue: No ]
  • Number of Participants With Viral Resistance [ Time Frame: Baseline up to Day 50 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: January 2014
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oseltamivir: Standard dose
Participants will receive standard dose of oseltamivir capsules or suspension orally for 5 to maximum of 20 days depending on weight. Infants <1 year of age will receive oseltamivir at a dose of 3 milligrams per kilogram (mg/kg).
Drug: Oseltamivir
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.
Other Name: Tamiflu
Experimental: Oseltamivir: Triple dose
Participants will receive three times the standard dose of oseltamivir capsules or suspension orally for 5 to maximum of 20 days depending on weight and age. Infants <1 year will receive standard dose at 3 mg/kg.
Drug: Oseltamivir
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.
Other Name: Tamiflu

  Eligibility

Ages Eligible for Study:   up to 12 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 <2 weeks of age or, if born pre-term, 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
  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: NCT01715909

Contacts
Contact: Reference Study ID Number: NV25719 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

  Show 49 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01715909     History of Changes
Other Study ID Numbers: NV25719  2012-002633-11 
Study First Received: October 25, 2012
Last Updated: September 14, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Oseltamivir
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 23, 2016