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

NCT00844155 | Withdrawn

• 2 other identifiers: #ML25018Contract ID # 17908C
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Influenza A Virus Infection; Influenza B Virus Infection

Keywords

Prevention or treatment of influenza in ventilated patients

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Test the hypothesis that increasing the dose (150 mg), with and without concomitant enteral feeding, will show a proportionate increase in bioavailability.

  13 months

Study Arms (2)

A.Oseltamivir 75 mg dose

ACTIVE COMPARATOR

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

B. Oseltamivir 150mg

ACTIVE COMPARATOR

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

Interventions

Oseltamivir 75 mg DRUG

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.

Also known as: Tamiflu

A.Oseltamivir 75 mg dose; B. Oseltamivir 150mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Manitoba: lead
• Hoffmann-La Roche: collaborator

Study Sites (1)

Health Sciences Centre

Winnipeg, Manitoba, R3E 0Z3, Canada

Location

MeSH Terms

Interventions

Oseltamivir

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Faisal Siddiqui, MD

  University of Manitoba

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator MD

Study Record Dates

• First Submitted: February 13, 2009
• First Posted: February 16, 2009
• Study Start: March 1, 2009
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: September 17, 2019

Record last verified: 2019-09

Locations

CA (1)