HIVPhase 4NCT01386970
Effect of Gender and HIV Infection on Zidovudine and Lamivudine Pharmacokinetics
A Phase 4 study testing zidovudine 300mg and lamivudine 150mg as Combivir in people with HIV, run by University of Colorado, Denver at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV
- What is being tested?
- zidovudine 300mg and lamivudine 150mg as Combivir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteUnited States
- Study dates
- May 2005to Jul 2010
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado Denver and Health Sciences Center
Aurora, Colorado, 80045
About this study
Official title: Sex and Disease Dependent Nucleoside Analog Toxicity
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
- Being tested
- zidovudine 300mg and lamivudine 150mg as Combivir
- Keywords
- Pharmacokinetics, antiretroviral therapy, nucleoside analogs, mitochondrial toxicity, clinical pharmacology, cellular pharmacology, pharmacogenetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
zidovudine 300mg and lamivudine 150mg as CombivirDrug
twice daily for 12 days in the HIV-negative group and indefinitely for their care in the HIV-positive group
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: zidovudine 300mg and lamivudine 150mg as Combivir |
What is being measured
The primary outcome is the main question the study is designed to answer.
ZDV-TP Drug Levels Compared Between HIV Negative and HIV Infected Subject
To compare ZDV- triphosphate concentrations in HIV-negative versus HIV-infected subjects.
Measured: 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.
Measured: Day 12 of dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2011 (estimated)
- Study startMay 2005
- Primary completionJul 2008
- Study completionJul 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), University of Hawaii
- Responsible party
- Sponsor
- Investigators
- Peter L. Anderson, PharmD, Principal investigator, University of Colorado Denver and Health Sciences Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01386970
- Sponsor's protocol ID
- 04-1101
- Other IDs
- R01AI064029
- Status last verified
- Mar 2020
- First submitted
- 28 Jun 2011
- Last updated
- 16 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: No plan to share.
Publications
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.
PubMed 19372976Anderson PL, Rower JE. Zidovudine and Lamivudine for HIV Infection. Clin Med Rev Ther. 2010;2:a2004.
PubMed 20953318Ghodke 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.
PubMed 22960662Rower 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.
PubMed 21465499Anderson 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.
PubMed 17721092Rower 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.
PubMed 22391541
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sex and Disease Dependent Nucleoside Analog Toxicity
- ClinicalTrials.gov ID
- NCT01386970
- Acronym / sponsor ID
- 04-1101
- Conditions
- HIV
- Keywords
- Pharmacokinetics, antiretroviral therapy, nucleoside analogs, mitochondrial toxicity, clinical pharmacology, cellular pharmacology, pharmacogenetics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), University of Hawaii
- Study start
- May 2005
- Primary completion
- Jul 2008 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 1 Jul 2011 (estimated)
- Results
- Posted 16 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HIV-negative | Active comparator | Drug: zidovudine 300mg and lamivudine 150mg as CombivirThis group was used to compare intracellular ZDV- and 3TC-triphosphate concentrations to the HIV-infected group and in men versus women. |
| HIV-infected | Active comparator | Drug: zidovudine 300mg and lamivudine 150mg as CombivirThis 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (9 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| zidovudine 300mg and lamivudine 150mg as Combivirtwice daily for 12 days in the HIV-negative group and indefinitely for their care in the HIV-positive group | Drug | HIV-infected, HIV-negative |
Primary outcome
ZDV-TP Drug Levels Compared Between HIV Negative and HIV Infected Subject
Time frame: Day 12 of dosing
To compare ZDV- triphosphate concentrations in HIV-negative versus HIV-infected subjects.
3TC-TP Drug Levels Compared Between HIV Negative and HIV Infected Subject
Time frame: Day 12 of dosing
To compare 3TC- triphosphate concentrations in HIV-negative versus HIV-infected subjects.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19372976Anderson 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.
- Background: PubMed 20953318Anderson PL, Rower JE. Zidovudine and Lamivudine for HIV Infection. Clin Med Rev Ther. 2010;2:a2004.
- Background: PubMed 22960662Ghodke 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.
- Results publication: PubMed 21465499Rower 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.
- Results publication: PubMed 17721092Anderson 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.
- Results publication: PubMed 22391541Rower 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.
- Individual participant dataSharing planned: No. No plan to share.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter L. Anderson, PharmD principal investigator
University of Colorado Denver and Health Sciences Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing zidovudine 300mg and lamivudine 150mg as Combivir in people with HIV, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ZDV-TP Drug Levels Compared Between HIV Negative and HIV Infected Subject (time frame: Day 12 of dosing). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01386970, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2020.