Zidovudine and Lamivudine Given Once Versus Twice Daily

HIV Infections Clinical Trial

Official title:

A Phase I Pharmacokinetic Study of Once Versus Twice Daily Dosing With Zidovudine and Lamivudine

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00014014
• Other study ID #: P1012
• Secondary ID: PACTG P1012ACTG
• Status: Completed
• Phase: Phase 1
• First received: April 7, 2001
• Last updated: October 4, 2013
• Est. completion date: August 2002

Study information

• Verified date: October 2013
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: August 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 24 Years

Eligibility

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.

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Lamivudine/Zidovudine

Locations

Country	Name	City	State
Puerto Rico	Univ of Puerto Rico / Univ Children's Hosp AIDS	San Juan
United States	Emory Univ Hosp / Pediatrics	Atlanta	Georgia
United States	Children's Hosp of Boston	Boston	Massachusetts
United States	Chicago Children's Memorial Hosp	Chicago	Illinois
United States	Cook County Hosp	Chicago	Illinois
United States	Mt Sinai Hosp Med Ctr / Dept of Pediatrics	Chicago	Illinois
United States	Texas Children's Hosp / Baylor Univ	Houston	Texas
United States	Univ of Mississippi Med Ctr	Jackson	Mississippi
United States	Univ of Florida Health Science Ctr / Pediatrics	Jacksonville	Florida
United States	Los Angeles County - USC Med Ctr	Los Angeles	California
United States	Saint Jude Children's Research Hosp of Memphis	Memphis	Tennessee
United States	Tulane Univ / Charity Hosp of New Orleans	New Orleans	Louisiana
United States	Metropolitan Hosp Ctr	New York	New York
United States	Univ of Medicine & Dentistry of New Jersey / Univ Hosp	Newark	New Jersey
United States	St Joseph's Hosp & Med Center	Paterson	New Jersey
United States	Children's Hosp of Philadelphia	Philadelphia	Pennsylvania
United States	Temple University School of Medicine	Philadelphia	Pennsylvania
United States	Univ of California, San Diego	San Diego	California
United States	State Univ of New York at Stony Brook	Stony Brook	New York
United States	SUNY Health Sciences Ctr at Syracuse / Pediatrics	Syracuse	New York

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (1)

Flynn PM, Rodman J, Lindsey JC, Robbins B, Capparelli E, Knapp KM, Rodriguez JF, McNamara J, Serchuck L, Heckman B, Martinez J; PACTG P1012 Team. Intracellular pharmacokinetics of once versus twice daily zidovudine and lamivudine in adolescents. Antimicro — View Citation

External Links

•   Click here for more information about Lamivudine/Zidovudine
•   Haga clic aquí para ver información sobre este ensayo clínico en español.