Zidovudine and Lamivudine Given Once Versus Twice Daily

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00014014
First received: April 7, 2001
Last updated: October 4, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Lamivudine/Zidovudine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Primary Purpose: Treatment
Official Title: A Phase I Pharmacokinetic Study of Once Versus Twice Daily Dosing With Zidovudine and Lamivudine

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 20
Study Completion Date: August 2002
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

Ages Eligible for Study:   12 Years to 24 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00014014

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

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00014014     History of Changes
Other Study ID Numbers: P1012, PACTG P1012, ACTG P1012, 11648
Study First Received: April 7, 2001
Last Updated: October 4, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Zidovudine
Phosphorylation
Drug Administration Schedule
Lamivudine
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Pharmacokinetics
Combivir

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Zidovudine
Lamivudine
Reverse Transcriptase Inhibitors
Lamivudine, zidovudine drug combination
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on August 27, 2014