Effect of Gender and HIV Infection on Zidovudine and Lamivudine Pharmacokinetics

NCT01386970 | Completed Phase 4 Results DMC

• 2 other identifiers: 04-1101R01AI064029
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluated the blood and blood cell concentrations of zidovudine and lamivudine in men versus women and in those with versus without HIV infection. Additionally, markers of side effects were correlated with blood levels of the drugs. The hypothesis was that women and those with HIV would have higher drug levels, as well as markers of side effects.

Conditions

HIV

Keywords

Pharmacokinetics; antiretroviral therapy; nucleoside analogs; mitochondrial toxicity; clinical pharmacology; cellular pharmacology; pharmacogenetics

Outcome Measures

Primary Outcomes (2)

• ZDV-TP Drug Levels Compared Between HIV Negative and HIV Infected Subject

  To compare ZDV- triphosphate concentrations in HIV-negative versus HIV-infected subjects.

  Day 12 of dosing

• 3TC-TP Drug Levels Compared Between HIV Negative and HIV Infected Subject

  To compare 3TC- triphosphate concentrations in HIV-negative versus HIV-infected subjects.

  Day 12 of dosing

Study Arms (2)

HIV-negative

ACTIVE COMPARATOR

This group was used to compare intracellular ZDV- and 3TC-triphosphate concentrations to the HIV-infected group and in men versus women.

Drug: zidovudine 300mg and lamivudine 150mg as Combivir

HIV-infected

ACTIVE COMPARATOR

This group was started on ZDV-3TC based therapy. Intracellular ZDV- and 3TC-triphosphate concentrations were compared in men versus women and the HIV-negative group.

Drug: zidovudine 300mg and lamivudine 150mg as Combivir

Interventions

zidovudine 300mg and lamivudine 150mg as Combivir DRUG

twice daily for 12 days in the HIV-negative group and indefinitely for their care in the HIV-positive group

HIV-infected; HIV-negative

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Documented physician-diagnosed HIV-infection (HIV+ antibody or plasma HIV-RNA+); HIV-negative volunteers must have a negative HIV-ELISA.
• Age 18 to 55 years;
• Either antiretroviral naïve, or no HIV-therapy in the preceding 6 months;
• Planned antiretroviral regimen includes standard doses of ZDV plus 3TC as part of the antiretroviral regimen. Once- or twice-daily 3TC will be allowed.

You may not qualify if:

• Any medical condition that in the opinion of the investigators would jeopardize the intent of the study.
• In the opinion of the investigator, any concomitant immunomodulatory medications, chemotherapeutic agents, investigational drugs, and alternative therapies, including, glucocorticoids, recombinant growth factors or cytokines (e.g. Granulocyte-macrophage colony-stimulating factor, Granulocyte colony-stimulating factor, interferon-alpha or gamma, human growth hormone, etc), ribavirin, birth-control pills, and sex hormones that could interfere with the cellular pharmacology of the study medications;
• Concomitant medications that interfere with renal drug clearances including, tenofovir, adefovir, cidofovir, ganciclovir, probenecid, or any similarly problematic medication in the opinion of the investigators;
• Concomitant warfarin or daily aspirin (to prevent excess bleeding from biopsy).
• Pregnancy or a plan to become pregnant, or menopause;
• Any \> or = grade II abnormality in hemoglobin, absolute neutrophil count, routine liver function tests, serum creatinine, or other organ function abnormalities.
• Any medical or personal condition that, in the judgment of the investigators, may influence the subject's ability to comply with study conditions, such as active mental illnesses, or plans to leave the geographical area.
• Inability to give informed consent.
• Triple nucleoside analog reverse transcriptase regimens.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• University of Hawaii: collaborator

Study Sites (1)

University of Colorado Denver and Health Sciences Center

Aurora, Colorado, 80045, United States

Location

Related Publications (6)

• Anderson PL. Recent developments in the clinical pharmacology of anti-HIV nucleoside analogs. Curr Opin HIV AIDS. 2008 May;3(3):258-65. doi: 10.1097/COH.0b013e3282f85dc1.

  PMID: 19372976 BACKGROUND

• Anderson PL, Rower JE. Zidovudine and Lamivudine for HIV Infection. Clin Med Rev Ther. 2010;2:a2004.

  PMID: 20953318 BACKGROUND

• Ghodke Y, Anderson PL, Sangkuhl K, Lamba J, Altman RB, Klein TE. PharmGKB summary: zidovudine pathway. Pharmacogenet Genomics. 2012 Dec;22(12):891-4. doi: 10.1097/FPC.0b013e32835879a8. No abstract available.

  PMID: 22960662 BACKGROUND

• Rower JE, Klein B, Bushman LR, Anderson PL. Validation of a sensitive LC/MS/MS method for the determination of zidovudine and lamivudine in human plasma. Biomed Chromatogr. 2012 Jan;26(1):12-20. doi: 10.1002/bmc.1617. Epub 2011 Apr 4.

  PMID: 21465499 RESULT

• Anderson PL, Zheng JH, King T, Bushman LR, Predhomme J, Meditz A, Gerber J, Fletcher CV. Concentrations of zidovudine- and lamivudine-triphosphate according to cell type in HIV-seronegative adults. AIDS. 2007 Sep 12;21(14):1849-54. doi: 10.1097/QAD.0b013e3282741feb.

  PMID: 17721092 RESULT

• Rower JE, Meditz A, Gardner EM, Lichtenstein K, Predhomme J, Bushman LR, Klein B, Zheng JH, Mawhinney S, Anderson PL. Effect of HIV-1 infection and sex on the cellular pharmacology of the antiretroviral drugs zidovudine and lamivudine. Antimicrob Agents Chemother. 2012 Jun;56(6):3011-9. doi: 10.1128/AAC.06337-11. Epub 2012 Mar 5.

  PMID: 22391541 RESULT

MeSH Terms

Interventions

Zidovudine; Lamivudine; lamivudine, zidovudine drug combination

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Zalcitabine; Deoxycytidine; Cytidine

Results Point of Contact

• Title: Dr. Peter Anderson
• Organization: University of Colorado | Skaggs School of Pharmacy and Pharmaceutical Sciences

peter.anderson@cuanschutz.edu

3037246128

Study Officials

• Peter L. Anderson, PharmD

  University of Colorado Denver and Health Sciences Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2011
• First Posted: July 1, 2011
• Study Start: May 1, 2005
• Primary Completion: July 1, 2008
• Study Completion: July 1, 2010
• Last Updated: March 16, 2020
• Results First Posted: March 16, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)