Zidovudine and Lamivudine Given Once Versus Twice Daily

October 4, 2013 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

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

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.

Study Overview

Status

Completed

Conditions

Intervention / 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.)

Study Type

Interventional

Enrollment

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • San Juan, Puerto Rico, 009365067
        • Univ of Puerto Rico / Univ Children's Hosp AIDS
  • United States
    • California
      • Los Angeles, California, United States, 90033
        • Los Angeles County - USC Med Ctr
      • San Diego, California, United States, 92103
        • Univ of California, San Diego
    • Florida
      • Jacksonville, Florida, United States, 32209
        • Univ of Florida Health Science Ctr / Pediatrics
    • Georgia
      • Atlanta, Georgia, United States, 30306
        • Emory Univ Hosp / Pediatrics
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Cook County Hosp
      • Chicago, Illinois, United States, 606143394
        • Chicago Children's Memorial Hosp
      • Chicago, Illinois, United States, 60608
        • Mt Sinai Hosp Med Ctr / Dept of Pediatrics
    • Louisiana
      • New Orleans, Louisiana, United States, 701122699
        • Tulane Univ / Charity Hosp of New Orleans
    • Massachusetts
      • Boston, Massachusetts, United States, 021155724
        • Children's Hosp of Boston
    • Mississippi
      • Jackson, Mississippi, United States, 39213
        • Univ of Mississippi Med Ctr
    • New Jersey
      • Newark, New Jersey, United States, 071032714
        • Univ of Medicine & Dentistry of New Jersey / Univ Hosp
      • Paterson, New Jersey, United States, 07503
        • St Joseph's Hosp & Med Center
    • New York
      • New York, New York, United States, 10029
        • Metropolitan Hosp Ctr
      • Stony Brook, New York, United States, 117948111
        • State Univ of New York at Stony Brook
      • Syracuse, New York, United States, 13210
        • SUNY Health Sciences Ctr at Syracuse / Pediatrics
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 191044318
        • Children's Hosp of Philadelphia
      • Philadelphia, Pennsylvania, United States, 19140
        • Temple University School of Medicine
    • Tennessee
      • Memphis, Tennessee, United States, 381052794
        • Saint Jude Children's Research Hosp of Memphis
    • Texas
      • Houston, Texas, United States, 77030
        • Texas Children's Hosp / Baylor Univ

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 24 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Interventional Model: Crossover Assignment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

  • Study Chair: Patricia Flynn

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (Actual)

August 1, 2002

Study Registration Dates

First Submitted

April 7, 2001

First Submitted That Met QC Criteria

August 30, 2001

First Posted (Estimate)

August 31, 2001

Study Record Updates

Last Update Posted (Estimate)

October 7, 2013

Last Update Submitted That Met QC Criteria

October 4, 2013

Last Verified

October 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P1012
  • 11648 (Registry Identifier: DAIDS ES)
  • PACTG P1012
  • ACTG P1012

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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