Study of the Relative Oral Bioavailability of the Antiflu Medicine Oseltamivir in the Intensive Care Unit

A Study of the Relative Oral Bioavailability of the Antiflu Medicine Oseltamivir (Tamiflu®) in Patients in the Intensive Care Unit

This proposed pharmacokinetic study will test the hypothesis that in critically ill patients with respiratory failure requiring mechanical ventilation such as might be anticipated to be needed to treat patients with severe influenza pneumonia, oseltamivir administered enterally via nasogastric tube, with and without concomitant food or alimentation, will have similar oral bioavailability to that observed in ambulatory adults ill with influenza in whom oseltamivir therapy 75 mg BID is efficacious and well tolerated. Additionally, this experiment will test the hypothesis that increasing the dose (150 mg), with and without concomitant enteral feeding, will show a proportionate increase in bioavailability. Relative oral bioavailability will be assessed from plasma concentration vs. time over 12 hrs and urinary recovery of drug from 0 to 48 hrs after administration.

Study Overview

• Status: Withdrawn
• Conditions: Influenza A Virus Infection; Influenza B Virus Infection
• Intervention / Treatment: Drug: Oseltamivir 75 mg

Detailed Description

Not required

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0Z3
      • Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients admitted to the Intensive Care Unit requiring mechanical ventilation due to respiratory failure
• must be within the ages of 18-75 yrs

Exclusion Criteria:

• patients unable to have enteral feeding
• intolerance to oseltamivir
• pregnancy
• gastrointestinal or malabsorptive disease
• intestinal bypass surgery
• diarrhea (>2 loose bowel movements per day)
• receipt of prokinetic medications (metoclopramide, domperidone, erythromycin)
• severe liver disease (hepatocellular enzymes > 3 times the upper limit of normal)
• renal failure (Cockroft-Gault Creatinine Clearance < 30 ml/min, Dialysis dependant)
• cystic fibrosis
• intoxication or drug overdose

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A.Oseltamivir 75 mg dose; Patients will be randomized to two groups (group A) to receive oseltamivir at 75 mg, or (group B) to receive the drug at 150 mg in the fasting or fed state.	Drug: Oseltamivir 75 mg; The primary objective of this study is to demonstrate that the pharmacokinetics of oseltamivir, when given enterally to critically ill patients, in the standard treatment dose of 75 mg or double that dose, 150 mg, will yield a plasma concentration - versus - Time Area under the curve (AUC) similar to that observed in adults with influenza treated successfully with a dose of 75 mg, that the disposition characteristics are dose proportionate and are not altered by the concomitant administration of enteral feedings.; Other Names: Tamiflu
Active Comparator: B. Oseltamivir 150mg; Patients will be randomized to groups (group A) to receive oseltamivir at 75 mg, or group B to receive the drug at 150 mg in the fasting or fed state.	Drug: Oseltamivir 75 mg; The primary objective of this study is to demonstrate that the pharmacokinetics of oseltamivir, when given enterally to critically ill patients, in the standard treatment dose of 75 mg or double that dose, 150 mg, will yield a plasma concentration - versus - Time Area under the curve (AUC) similar to that observed in adults with influenza treated successfully with a dose of 75 mg, that the disposition characteristics are dose proportionate and are not altered by the concomitant administration of enteral feedings.; Other Names: Tamiflu

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Oseltamivir administered enterally via nasogastric tube, with and without concomitant food or alimentation, will have similar oral bioavailability to that observed in ambulatory adults .	13 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Test the hypothesis that increasing the dose (150 mg), with and without concomitant enteral feeding, will show a proportionate increase in bioavailability.	13 months

Collaborators and Investigators

• Sponsor: University of Manitoba
• Collaborators: Hoffmann-La Roche
• Investigators: Principal Investigator: Faisal Siddiqui, MD, University of Manitoba

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Anticipated): July 1, 2009
• Study Completion (Anticipated): July 1, 2009

Study Registration Dates

• First Submitted: February 13, 2009
• First Submitted That Met QC Criteria: February 13, 2009
• First Posted (Estimate): February 16, 2009

Study Record Updates

• Last Update Posted (Actual): September 17, 2019
• Last Update Submitted That Met QC Criteria: September 14, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Prevention or treatment of influenza in ventilated patients
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Disease Attributes; DNA Virus Infections; Orthomyxoviridae Infections; Infections; Communicable Diseases; Virus Diseases; Influenza, Human; Herpesviridae Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Oseltamivir
• Other Study ID Numbers: #ML25018; Contract ID # 17908C