Pharmacokinetic Study of Oseltamivir and Intravenous Zanamivir in Healthy Adults

NCT00921726 | Completed Phase 1 DMC

• 1 other identifier: SEA 003
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

Due in part to widespread availability of oseltamivir and clinical experience using oseltamivir to treat H5N1 influenza virus infections, many strains of influenza have become resistant to it. Other reliable methods of treating H5N1 must be identified in case of a pandemic. One such option is intravenous zanamivir used in combination with oseltamivir. The primary purpose of this study is to evaluate the interaction between oral oseltamivir and intravenous zanamivir administered as either a continuous or intermittent infusion in healthy adults.

Conditions

Influenza; Virus Diseases

Keywords

Drug Interaction

Outcome Measures

Primary Outcomes (1)

• Oseltamivir carboxylate Cmax and AUC (0-12)

  Throughout study

Secondary Outcomes (3)

• Zanamivir Cmax and AUC (0-12) for continuous infusion and Zanamivir Cmax, AUC (-12), and C12 for intermittent infusions

  Throughout study

• Oseltamivir Cmax, AUC (0-12), and C12

  Throughout study

• Oseltamivir carboxylate AUC (0-24), C12, delta-z, and t(1/2)

  Throughout study

Study Arms (2)

1

EXPERIMENTAL

Participants will receive treatment in the following order: Study Regimens A, B, C, D

Drug: Zanamivir; Drug: Oseltamivir

2

EXPERIMENTAL

Participants will receive treatment in the following order: Study Regimens B, A, C, D

Drug: Zanamivir; Drug: Oseltamivir

Interventions

Zanamivir DRUG

Continuous (800 mg in Regimen A, 3600 mg in Regimen C) and intermittent (3600 mg in Regimen D) infusion

Also known as: Relenza

1; 2

Oseltamivir DRUG

150 mg oral tablets taken five times over 3 days in Regimens A, B, C, and D

Also known as: Tamiflu

1; 2

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Good general health
• Body mass index between 17 - 32 kg/m\^2
• Body weight of at least 37 kg
• Able to read, comprehend, and write at a sufficient level to complete study-related materials
• Normal ECG with QTC less than 450 msec as judged by cardiologist
• Willing and ability to comply with the study protocol for the duration of the trial

You may not qualify if:

• History of cardiac disease or abnormality. More information on this criterion can be found in the protocol.
• Family history of sudden cardiac death
• HIV-infected
• Hepatitis C virus infected
• Positive for hepatitis B surface antigen (HBsAg)
• History of renal disease, hepatic disease, and/or cholecystectomy
• Evidence of active substance abuse
• History of alcohol or substance abuse or dependence within 6 months prior to study entry. More information on this criterion can be found in the protocol.
• Use of prescription or non-prescription drugs, except paracetamol, at doses of up to 2 g/day. More information on this criterion can be found in the protocol.
• Use of FluMist, inactivated influenza vaccine, or any other anti-influenza antiviral medications within 14 days prior to study entry
• Participated in a clinical trial and received a drug or new chemical entity within 30 days or five half-lives prior to study entry.
• Unwilling to abstain from ingesting alcohol within 48 hours prior to study entry until collection of the final pharmacokinetic sample during each period
• Donated blood to the extent that participation in this study would result in excess of 300 mL donated within a 30 day period
• History of allergy to the study drug or drugs of this class. More information on this criterion can be found in the protocol.
• Unstable medical condition that, in the opinion of the investigator, would interfere with the study

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Johns Hopkins Bloomberg School of Public Health: collaborator

Study Sites (1)

Mathidol University

Salaya, 73170, Thailand

Location

Related Publications (3)

• Beigel J, Bray M. Current and future antiviral therapy of severe seasonal and avian influenza. Antiviral Res. 2008 Apr;78(1):91-102. doi: 10.1016/j.antiviral.2008.01.003. Epub 2008 Feb 4.

  PMID: 18328578 BACKGROUND

• Hata K, Koseki K, Yamaguchi K, Moriya S, Suzuki Y, Yingsakmongkon S, Hirai G, Sodeoka M, von Itzstein M, Miyagi T. Limited inhibitory effects of oseltamivir and zanamivir on human sialidases. Antimicrob Agents Chemother. 2008 Oct;52(10):3484-91. doi: 10.1128/AAC.00344-08. Epub 2008 Aug 11.

  PMID: 18694948 BACKGROUND

• Tappenden P, Jackson R, Cooper K, Rees A, Simpson E, Read R, Nicholson K. Amantadine, oseltamivir and zanamivir for the prophylaxis of influenza (including a review of existing guidance no. 67): a systematic review and economic evaluation. Health Technol Assess. 2009 Feb;13(11):iii, ix-xii, 1-246. doi: 10.3310/hta13110.

  PMID: 19215705 BACKGROUND

MeSH Terms

Conditions

Influenza, Human; Virus Diseases

Interventions

Zanamivir; Oseltamivir

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Sialic Acids; Neuraminic Acids; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Hydroxy Acids; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Amino Sugars; Carbohydrates; Acetamides; Amides; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Sasithon Pukrittayakamee, MD

  Mathidol University, Thailand

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH

Study Record Dates

• First Submitted: June 12, 2009
• First Posted: June 16, 2009
• Study Start: July 1, 2009
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: March 19, 2010

Record last verified: 2009-05

Locations

TH (1)