Zidovudine and Lamivudine Given Once Versus Twice Daily
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: Lamivudine/Zidovudine (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s): Patricia Flynn, Study Chair
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.
Clinical Details
Official title: A Phase I Pharmacokinetic Study of Once Versus Twice Daily Dosing With Zidovudine and Lamivudine
Study design: Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Primary Purpose: Treatment
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.)
Eligibility
Minimum age: 12 Years.
Maximum age: 24 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria
Patients may be eligible for this study if they:
- Are 12 through 24 years of age.
- Are HIV-positive.
- Weigh more than 40 kg.
- Have a CD4 cell count above 250 cells/microL.
- Have taken at least 4 weeks of 3 or more anti-HIV medications, which must include ZDV
and 3TC (as individual drugs or Combivir) and either a protease inhibitor or
nonnucleoside reverse transcriptase inhibitor, and do not plan to change these
medications during the study period.
- Have consent of a parent or guardian if under 18 years of age.
- Have a negative pregnancy test, if female and able to have children.
- Agree to use 2 effective methods of birth control (birth control pills plus a barrier
method or 2 barrier methods) while taking study medication, if female and able to
have children.
Exclusion Criteria
Patients will not be eligible for this study if they:
- Have an opportunistic (AIDS-related) infection that requires treatment at study
entry.
- Are receiving anti-cancer medications for cancer.
- Are taking certain anti-HIV medications (nucleoside or nucleotide reverse
transcriptase inhibitors, other than ZDV and 3TC), or hydroxyurea.
- Are pregnant or breast-feeding.
- Have diseases (other than HIV infection) or other conditions that, in the
investigator's opinion, would interfere with the study.
Locations and Contacts
Univ of Puerto Rico / Univ Children's Hosp AIDS, San Juan 009365067, Puerto Rico
Los Angeles County - USC Med Ctr, Los Angeles, California 90033, United States
Univ of California, San Diego, San Diego, California 92103, United States
Univ of Florida Health Science Ctr / Pediatrics, Jacksonville, Florida 32209, United States
Emory Univ Hosp / Pediatrics, Atlanta, Georgia 30306, United States
Chicago Children's Memorial Hosp, Chicago, Illinois 606143394, United States
Cook County Hosp, Chicago, Illinois 60612, United States
Mt Sinai Hosp Med Ctr / Dept of Pediatrics, Chicago, Illinois 60608, United States
Tulane Univ / Charity Hosp of New Orleans, New Orleans, Louisiana 701122699, United States
Children's Hosp of Boston, Boston, Massachusetts 021155724, United States
Univ of Mississippi Med Ctr, Jackson, Mississippi 39213, United States
Univ of Medicine & Dentistry of New Jersey / Univ Hosp, Newark, New Jersey 071032714, United States
St Joseph's Hosp & Med Center, Paterson, New Jersey 07503, United States
Metropolitan Hosp Ctr, New York, New York 10029, United States
State Univ of New York at Stony Brook, Stony Brook, New York 117948111, United States
SUNY Health Sciences Ctr at Syracuse / Pediatrics, Syracuse, New York 13210, United States
Children's Hosp of Philadelphia, Philadelphia, Pennsylvania 191044318, United States
Temple University School of Medicine, Philadelphia, Pennsylvania 19140, United States
Saint Jude Children's Research Hosp of Memphis, Memphis, Tennessee 381052794, United States
Texas Children's Hosp / Baylor Univ, Houston, Texas 77030, United States
Additional Information
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Last updated: October 4, 2013
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