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

Sponsor

University of Manitoba (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00844155

Collaborator

Hoffmann-La Roche (Industry)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Influenza A Virus Infection Influenza B Virus Infection	Drug: Oseltamivir 75 mg	N/A

Detailed Description

Not required

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

None (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

Study Start Date :

Mar 1, 2009

Anticipated Primary Completion Date :

Jul 1, 2009

Anticipated Study Completion Date :

Jul 1, 2009

Arms and Interventions

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

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

Other Names:

Tamiflu

Outcome Measures

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 . [13 months]

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. [13 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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