Pharmacokinetic Study of Oseltamivir and Intravenous Zanamivir in Healthy Adults
Condition: Influenza; Virus Diseases
MeSH terms: Virus Diseases
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      It is very likely that during an influenza pandemic, intravenous zanamivir will be used in
      combination with oseltamivir. Although the potential for a drug interaction between the two
      drugs is very low, the likelihood of coadministration combined with the common route of renal
      clearance of both drugs and the current lack of information on the organic anion transporter
      polypeptides (OATP) inhibition potential of zanamivir in vivo warrants verification of a lack
      of an interaction. This study will provide clinical guidance for the use of intravenous
      zanamivir in settings where oral oseltamivir is commonly used, such as areas in which human
      cases of H5N1 have been reported.

      The total duration of study participation is approximately 13 weeks. Each participant will
      have a screening visit, four treatment steps, and a follow-up visit. The screening visit to
      determine enrollment eligibility will be conducted within 45 days prior to receiving the
      first dose. Participants will be randomized to receive either Regimen A or B for Step 1.
      Participants who received Regimen A will receive Regimen B in Step 2 and vice versa. After
      completing Step 2, all participants will continue with Regimens C and D, consecutively, in
      Steps 3 and 4, with at least 3 days between each step. A follow-up visit will occur 7-10 days
      after completing the last treatment assessments or withdrawing from the study.

      Regimen A consists of continuous intravenous zanamivir infusion (800 mg) for 16 hours.
      Regimen B consists of 150 mg oral oseltamivir tablets taken five times over 3 days. Regimen C
      consists of 150 mg oral oseltamivir tablets taken five times over 3 days plus continuous
      intravenous zanamivir infusion (3600 mg) for 36 hours. Regimen D consists of 150 mg oral
      oseltamivir tablets taken five times over 3 days plus intermittent intravenous zanamivir
      infusion received in five 30 minute intervals (3000 mg total).

      Blood and urine collection, vital signs, pharmacokinetic sampling, adverse event assessment,
      and pregnancy test for females will occur at each step in the study. The follow-up visit will
      involve blood and urine collection, vital signs, adverse event assessment, and pregnancy test
      for females.
    

Intervention name(s): Zanamivir; Oseltamivir
Intervention type(s): Drug; Drug
Intervention description(s): Continuous (800 mg in Regimen A, 3600 mg in Regimen C) and intermittent (3600 mg in Regimen D) infusion; 150 mg oral tablets taken five times over 3 days in Regimens A, B, C, and D
Other intervention name(s): Relenza; Tamiflu
Intervention MeSH terms: Oseltamivir; Zanamivir
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Drug Interaction