DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



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

Click here for more information about Lamivudine/Zidovudine

Haga clic aquí para ver información sobre este ensayo clínico en español.


Last updated: October 4, 2013

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017