Alternative Oseltamivir Dosing Strategies
This study will determine if oseltamivir (Tamiflu(Registered Trademark)) is safe and effective given less frequently than the currently prescribed dose of twice a day for 5 days to people who have the flu, and once a day for up to 6 weeks in people who have been exposed to someone else with flu and want to prevent getting it themselves. This study will see if the drug can be given once every other day instead of daily if given with another medication called probenecid (Benemid(Registered Trademark) or Probalan(Registered Trademark)).
Healthy people 18 years of age and older may be eligible for this study. Candidates are screened with a medical history, physical examination, and blood and urine tests.
Participants are randomly assigned to one of the following regimens for 2 weeks: 1) 75 milligrams (mg) of oseltamivir once a day; 2) 75 mg of oseltamivir once every other day plus 500 mg probenecid four times a day; or 3) 75 mg of oseltamivir once every other day plus 500 mg probenecid twice a day. All medications are taken by mouth. On study day 0, subjects have the following baseline procedures: measurement of vital signs, review of medical and medication history, physical examination, blood draw and urine test. They also receive the first dose of oseltamivir or oseltamivir and probenecid. In addition, they undergo the following procedures as follows:
- Days 1 and 4: Vital signs; review of clinical symptoms, side effects and medications taken; urine testing and blood draw.
- Day 8: Same as day 1 plus count of study medication.
- Day 14: Same as day 8 plus pharmacokinetic study to measure the amount of oseltamivir and probenecid in the blood. For this test, a catheter is inserted into an arm vein and blood samples are collected through the catheter before taking the study medications, at the time the medications are taken, and again at 15 minutes, 30 minutes, 45 minutes and 1, 1.5, 2, 4, 8 and 12 hours after the medication is taken. The catheter is then removed. This is the last day to take the study medication.
- Day 15: Blood draw for 24-hour (post medication) blood sample.
- Day 16: Blood draw for 48-hour (post medication) blood sample.
- Days 21 and 28: Same as day 1.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||Evaluation of Alternative Oseltamivir (Tamiflu[R]) Dosing Strategies for Use During Influenza Prophylaxis|
|Study Start Date:||June 2006|
|Study Completion Date:||April 2007|
|Primary Completion Date:||April 2007 (Final data collection date for primary outcome measure)|
Pandemic influenza infection has the potential for causing significant morbidity and mortality in the United States and elsewhere. Oseltamivir (Tamiflu[R]) is a selective inhibitor of influenza virus neuraminidase and is U.S. FDA approved for both treatment and prophylaxis against influenza A and B viruses. However, at a time of national emergency, the supply of oseltamivir may be limited and alternative dosing strategies may be needed in order to provide as wide protection as possible from influenza or to treat as many infected patients as possible. Agents such as Probenecid that may extend the half-life of oseltamivir while maintaining effective oseltamivir plasma levels may potentially be useful in this regard. In this multi-center, three-arm, open-label, 48 patient trial, we propose to explore the relative safety and pharmacokinetics of oseltamivir plus Probenecid for 14 days in normal volunteers above and below the age of 65, according to the following dosing strategies: 16 subjects will be assigned to Group I Control Arm (Tamiflu[R] 75 mg given orally once daily), 16 subjects will be assigned to Group II Treatment Arm (Tamiflu [R] 75 mg orally once every other day plus Probenecid 500 mg orally four times daily), and 16 subjects will be assigned to Group III Treatment Arm (Tamiflu[R] 75 mg orally every other day and Probenecid 500 mg orally twice daily).
|United States, California|
|VA Greater Los Angeles Healthcare System|
|Los Angeles, California, United States, 94304|
|VA Palo Alto Health Care System|
|Palo Alto, California, United States, 94304|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|United States, Texas|
|Brooke Army Medical Center|
|Houston, Texas, United States|