Zidovudine and Lamivudine Given Once Versus Twice Daily
- Conditions
- HIV Infections
- Registration Number
- NCT00014014
- Brief Summary
The purpose of this study is to see if the full daily dose of Combivir (zidovudine \[ZDV\]/lamivudine \[3TC\]) taken once a day is as effective as the usual recommended twice-a-day dose.
Studies have shown that the antiviral activity of ZDV can continue in the body even after there does not appear to be any ZDV left in the blood. This occurs because the body breaks down the drug into substances that remain active against HIV. The body also breaks down 3TC, a drug that is combined with ZDV in the Combivir product, in a similar way. Since antiviral activity may continue after Combivir is removed from the body, it may not be necessary to take the drug as often as once thought. This study carefully measures levels of the active substances in order to find out whether the same amount of antiviral activity occurs with less-frequent dosing.
- Detailed Description
Initial dosing regimens of ZDV were based on the plasma half-life of the drug. However, recent studies of the intracellular metabolism of ZDV have demonstrated that the active anabolite, ZDV-TP, is present within the cell for an extended period of time relative to the drug in the plasma. This suggests that antiviral activity may be present for a sufficient time frame with less-frequent dosing of the drug. Careful comparison of the rate and extent of intracellular phosphorylated ZDV metabolites as a function of schedule will determine whether less-frequent dosing has a sound pharmacological basis. Also, the intracellular metabolism of 3TC is via different enzymes than that of ZDV and there are quantitative differences in the amount of triphosphate formed from both drugs. This study will provide information about intracellular metabolites when both ZDV and 3TC are concurrently administered.
This is a study of 2 schedules of Combivir therapy. At study entry or Part I, all patients take Combivir twice daily for the 7-day adherence assessment. Patients who have demonstrated 70 percent or greater adherence \[AS PER AMENDMENT 7/20/01: 70 percent compliance with the study regimen for Combivir. This corresponds to taking at least 10 of the prescribed 14 Combivir tablets during the 7 days prior to an adherence assessment, including all scheduled doses in the 24-hour period prior to that assessment.\], and have taken all scheduled Combivir doses in the previous 24 hours, have pharmacokinetic samples obtained and are randomized to Group A or Group B in Part II. Group A patients take 2 Combivir tablets once daily; Group B patients take 1 Combivir tablet twice daily. After patients have completed the targeted duration of Part II (7 days for Group A and 7-14 days for Group B), they are assessed for adherence. Patients who have demonstrated 70 percent or greater adherence, and have taken all scheduled Combivir doses in the previous 24 hours, have pharmacokinetic samples obtained and then change to the alternate dosing schedule. Group A patients take 1 Combivir tablet twice daily; Group B patients take 2 Combivir tablets once daily. After patients have completed the targeted duration of Part III (7-14 days for Group A and 7 days for Group B), they are assessed for adherence. All patients who meet the adherence criteria have pharmacokinetic samples obtained. After completion of Part III pharmacokinetic studies, patients have completed the study. (Note: Combivir will not be provided in this study.)
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 20
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (20)
State Univ of New York at Stony Brook
🇺🇸Stony Brook, New York, United States
Temple University School of Medicine
🇺🇸Philadelphia, Pennsylvania, United States
Univ of Mississippi Med Ctr
🇺🇸Jackson, Mississippi, United States
Univ of Medicine & Dentistry of New Jersey / Univ Hosp
🇺🇸Newark, New Jersey, United States
Tulane Univ / Charity Hosp of New Orleans
🇺🇸New Orleans, Louisiana, United States
Univ of Puerto Rico / Univ Children's Hosp AIDS
🇵🇷San Juan, Puerto Rico
Saint Jude Children's Research Hosp of Memphis
🇺🇸Memphis, Tennessee, United States
Texas Children's Hosp / Baylor Univ
🇺🇸Houston, Texas, United States
Univ of California, San Diego
🇺🇸San Diego, California, United States
Children's Hosp of Boston
🇺🇸Boston, Massachusetts, United States
Los Angeles County - USC Med Ctr
🇺🇸Los Angeles, California, United States
Emory Univ Hosp / Pediatrics
🇺🇸Atlanta, Georgia, United States
Univ of Florida Health Science Ctr / Pediatrics
🇺🇸Jacksonville, Florida, United States
Mt Sinai Hosp Med Ctr / Dept of Pediatrics
🇺🇸Chicago, Illinois, United States
Metropolitan Hosp Ctr
🇺🇸New York, New York, United States
Chicago Children's Memorial Hosp
🇺🇸Chicago, Illinois, United States
Children's Hosp of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Cook County Hosp
🇺🇸Chicago, Illinois, United States
SUNY Health Sciences Ctr at Syracuse / Pediatrics
🇺🇸Syracuse, New York, United States
St Joseph's Hosp & Med Center
🇺🇸Paterson, New Jersey, United States