Zidovudine and Lamivudine Given Once Versus Twice Daily

NCT ID: NCT00014014

Last Updated: 2013-10-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Completion Date

2002-08-31

Brief Summary

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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

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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.)

Conditions

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HIV Infections

Keywords

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Zidovudine Phosphorylation Drug Administration Schedule Lamivudine Reverse Transcriptase Inhibitors Anti-HIV Agents Pharmacokinetics Combivir

Study Design

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Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Interventions

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Lamivudine/Zidovudine

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

12 Years

Maximum Eligible Age

24 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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

NIH

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Patricia Flynn

Role: STUDY_CHAIR

Locations

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Metropolitan Hosp Ctr

New York, New York, United States

Site Status

Los Angeles County - USC Med Ctr

Los Angeles, California, United States

Site Status

Univ of California, San Diego

San Diego, California, United States

Site Status

Univ of Florida Health Science Ctr / Pediatrics

Jacksonville, Florida, United States

Site Status

Emory Univ Hosp / Pediatrics

Atlanta, Georgia, United States

Site Status

Mt Sinai Hosp Med Ctr / Dept of Pediatrics

Chicago, Illinois, United States

Site Status

Cook County Hosp

Chicago, Illinois, United States

Site Status

Chicago Children's Memorial Hosp

Chicago, Illinois, United States

Site Status

Tulane Univ / Charity Hosp of New Orleans

New Orleans, Louisiana, United States

Site Status

Children's Hosp of Boston

Boston, Massachusetts, United States

Site Status

Univ of Mississippi Med Ctr

Jackson, Mississippi, United States

Site Status

Univ of Medicine & Dentistry of New Jersey / Univ Hosp

Newark, New Jersey, United States

Site Status

St Joseph's Hosp & Med Center

Paterson, New Jersey, United States

Site Status

State Univ of New York at Stony Brook

Stony Brook, New York, United States

Site Status

SUNY Health Sciences Ctr at Syracuse / Pediatrics

Syracuse, New York, United States

Site Status

Children's Hosp of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Temple University School of Medicine

Philadelphia, Pennsylvania, United States

Site Status

Saint Jude Children's Research Hosp of Memphis

Memphis, Tennessee, United States

Site Status

Texas Children's Hosp / Baylor Univ

Houston, Texas, United States

Site Status

Univ of Puerto Rico / Univ Children's Hosp AIDS

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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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. Antimicrob Agents Chemother. 2007 Oct;51(10):3516-22. doi: 10.1128/AAC.01626-06. Epub 2007 Jul 30.

Reference Type RESULT
PMID: 17664328 (View on PubMed)

Other Identifiers

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PACTG P1012

Identifier Type: -

Identifier Source: secondary_id

ACTG P1012

Identifier Type: -

Identifier Source: secondary_id

11648

Identifier Type: REGISTRY

Identifier Source: secondary_id

P1012

Identifier Type: -

Identifier Source: org_study_id