HIV InfectionsPhase 1NCT00014014
Zidovudine and Lamivudine Given Once Versus Twice Daily
A Phase 1 study testing Lamivudine/Zidovudine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 20 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 12 to 24 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- Lamivudine/Zidovudine
- How many people
- 20 participants
- Where
- 20 sitesin 2 countries
- Study dates
- Start not givento Aug 2002
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 12 to 24 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Show all 9Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
20 sites in 2 countries.
20 sites in 2 countries
United States19 sites
Emory Univ Hosp / Pediatrics
Atlanta, Georgia, 30306
Children's Hosp of Boston
Boston, Massachusetts, 021155724
Mt Sinai Hosp Med Ctr / Dept of Pediatrics
Chicago, Illinois, 60608
Cook County Hosp
Chicago, Illinois, 60612
Chicago Children's Memorial Hosp
Chicago, Illinois, 606143394
Texas Children's Hosp / Baylor Univ
Houston, Texas, 77030
Univ of Mississippi Med Ctr
Jackson, Mississippi, 39213
Univ of Florida Health Science Ctr / Pediatrics
Jacksonville, Florida, 32209
Los Angeles County - USC Med Ctr
Los Angeles, California, 90033
Saint Jude Children's Research Hosp of Memphis
Memphis, Tennessee, 381052794
Tulane Univ / Charity Hosp of New Orleans
New Orleans, Louisiana, 701122699
Metropolitan Hosp Ctr
New York, New York, 10029
Univ of Medicine & Dentistry of New Jersey / Univ Hosp
Newark, New Jersey, 071032714
St Joseph's Hosp & Med Center
Paterson, New Jersey, 07503
Children's Hosp of Philadelphia
Philadelphia, Pennsylvania, 191044318
Temple University School of Medicine
Philadelphia, Pennsylvania, 19140
Univ of California, San Diego
San Diego, California, 92103
State Univ of New York at Stony Brook
Stony Brook, New York, 117948111
SUNY Health Sciences Ctr at Syracuse / Pediatrics
Syracuse, New York, 13210
Puerto Rico1 site
Univ of Puerto Rico / Univ Children's Hosp AIDS
San Juan, 009365067
About this study
Official title: 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.
Read the 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.)
- Conditions
- HIV Infections
- Being tested
- Lamivudine/Zidovudine
- Keywords
- Zidovudine, Phosphorylation, Drug Administration Schedule, Lamivudine, Reverse Transcriptase Inhibitors, Anti-HIV Agents, Pharmacokinetics, Combivir
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lamivudine/ZidovudineDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
- Study completionAug 2002
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The 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 1
- Primary purpose
- Treatment
- Intervention model
- Crossover
- Enrolment
- 20 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Patricia Flynn, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00014014
- Sponsor's protocol ID
- P1012
- Other IDs
- PACTG P1012, ACTG P1012, 11648
- Status last verified
- Oct 2013
- First submitted
- 7 Apr 2001
- Last updated
- 7 Oct 2013
- Results posted
- No
Publications
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.
PubMed 17664328
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Pharmacokinetic Study of Once Versus Twice Daily Dosing With Zidovudine and Lamivudine
- ClinicalTrials.gov ID
- NCT00014014
- Acronym / sponsor ID
- P1012
- Conditions
- HIV Infections
- Keywords
- Zidovudine, Phosphorylation, Drug Administration Schedule, Lamivudine, Reverse Transcriptase Inhibitors, Anti-HIV Agents, Pharmacokinetics, Combivir
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study completion
- Aug 2002 (actual)
- First posted
- 31 Aug 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Intervention model
- Crossover
Who may qualify
- Ages
- 12 to 24 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
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 |
|---|---|---|
| Lamivudine/Zidovudine | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2013.
- Results publication: PubMed 17664328Flynn 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.
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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.
Patricia Flynn study chair
20 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lamivudine/Zidovudine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 20 sites in 2 countries.
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 9 inclusion and 6 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 7 Oct 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, Puerto Rico. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00014014, which also lists 1 linked publication.
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 7 Oct 2013.