Study of the Relative Oral Bioavailability of the Antiflu Medicine Oseltamivir in the Intensive Care Unit - Full Text View

Purpose

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.

Condition	Intervention
Influenza A Virus Infection Influenza B Virus Infection	Drug: Oseltamivir 75 mg

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Bio-availability Study Intervention Model: Factorial Assignment Masking: Open Label Primary Purpose: Basic Science
Official Title:	A Study of the Relative Oral Bioavailability of the Antiflu Medicine Oseltamivir (Tamiflu®) in Patients in the Intensive Care Unit

Resource links provided by NLM:

MedlinePlus related topics: Flu

Drug Information available for: Oseltamivir Oseltamivir phosphate

U.S. FDA Resources

Further study details as provided by University of Manitoba:

Primary Outcome Measures:

Oseltamivir administered enterally via nasogastric tube, with and without concomitant food or alimentation, will have similar oral bioavailability to that observed in ambulatory adults . [ Time Frame: 13 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Test the hypothesis that increasing the dose (150 mg), with and without concomitant enteral feeding, will show a proportionate increase in bioavailability. [ Time Frame: 13 months ] [ Designated as safety issue: No ]

Enrollment:	0
Study Start Date:	March 2009
Estimated Study Completion Date:	July 2009
Estimated Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Name: 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 Name: Tamiflu

Arms

Assigned Interventions

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 Name: 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 Name: Tamiflu

Detailed Description:

Not required

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00844155

Locations

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

Sponsors and Collaborators

University of Manitoba

Hoffmann-La Roche

Investigators

Principal Investigator:

Faisal Siddiqui, MD

University of Manitoba

More Information

No publications provided

Responsible Party:	Faisal Siddiqui MD, University of Manitoba
ClinicalTrials.gov Identifier:	NCT00844155 History of Changes
Other Study ID Numbers:	#ML25018, Contract ID # 17908C
Study First Received:	February 13, 2009
Last Updated:	April 1, 2010
Health Authority:	Canada: Health Canada

Keywords provided by University of Manitoba:

Prevention or treatment of influenza in ventilated patients

Additional relevant MeSH terms:

Influenza, Human
Encephalitis, Herpes Simplex
Virus Diseases
Orthomyxoviridae Infections
RNA Virus Infections
Respiratory Tract Infections
Respiratory Tract Diseases
Encephalitis, Viral
Encephalitis
Central Nervous System Viral Diseases
Herpesviridae Infections

DNA Virus Infections
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Oseltamivir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 19, 2013