HIVPhase 4NCT00335192
To Determine if There Are Pharmacokinetic Interactions at Plasma or Intracellular Level Between Nucleosides and Tenofovir
A Phase 4 study testing Patients in treatment with 3TC + TDF + LPV/rtv, stop tenofovir during 4 weeks, Patients in treatment with ABV + TDF + LPV/rtv, stop tenofovir during 4 weeks and Patients in treatment with 3TC + ABV + TDF+ LPV/rtv, stop TDF during 4 weeks in people with HIV, run by Germans Trias i Pujol Hospital at 1 site in Spain.
Trial summary
The purpose of this study is to evaluate if there are pharmacokinetic interactions between the NRTI 3TC and ABV, and the TDF nucleotide. For this purpose, the intracellular and plasma levels of 3TC and ABV will be compared in patients given these nucleosides with TDF and 30 days after the interruption of the TDF. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- HIV
- What is being tested?
- Patients in treatment with 3TC + TDF + LPV/rtv, stop tenofovir during 4 weeks, Patients in treatment with ABV + TDF + LPV/rtv, stop tenofovir during 4 weeks and Patients in treatment with 3TC + ABV + TDF+ LPV/rtv, stop TDF during 4 weeks
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteSpain
- Study dates
- Jan 2005to Sep 2005
- Phase
- Phase 4
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV+ patients aged above 18 years.
- Undetectable HIV viral load in the last determination
- Patients capable of correct compliance according to clinical criteria.
- Patients on triple HAART therapy for the previous 3 months including 3TC and/or ABV and TDF, with a PI (Lopinavir/ritonavir) or an NNRTI (Nevirapine)
- Women may not be of fertile age (defined as at least one year from menopause or undergoing any surgical sterilisation technique), or must undertake to use a barrier contraceptive method during the study.
- Ability to provide informed consent.
Who cannot join
- Incorrect therapeutic compliance over the four weeks before the beginning of the study.
- Interruption or withdrawal from therapy during follow-up.
- Concomitant treatment with any drug which according to the clinician's criterion may interact with the investigational antiretrovirals, such as other antiretrovirals.
- Triple HAART therapy including Nevirapine (for phase II)
- Documented or suspected resistance to ABV, 3TC or lopinavir/rtv (for phase II).
Trial locations and contacts
1 site in 1 country.
Spain1 site
Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, 08916
About this study
Official title: Determination of Plasma and Intracellular Levels of Nucleoside Reverse Transcriptase Inhibitors (NRTI) and of Nucleotide Analog Tenofovir Disoproxil Fumarate (TDF) in Patients Treated With Abacavir and/or Lamivudine Given With or Without TDF.
The purpose of this study is to evaluate if there are pharmacokinetic interactions between the NRTI 3TC and ABV, and the TDF nucleotide. For this purpose, the intracellular and plasma levels of 3TC and ABV will be compared in patients given these nucleosides with TDF and 30 days after the interruption of the TDF.
Read the detailed description
There is clear evidence of pharmacokinetic interaction between ddI+TDF. However, the interaction between TDF and other NRTIs, mainly at intracellular level, has not been so well studied.
Since all the NRTIs are anabolized at intracellular level by numerous kinases, and are transported by passive carrier systems, the interaction may be between TDF and other NRTIs.
This study aims to investigate the pharmacokinetic interactions between the TDF and the nucleosides abacavir (ABV) and lamivudine (3TC) at plasma and intracellular level.
With this objective, intracellular and plasma levels will be analysed in a group of patients that receive the combinations 3TC +TDF, ABV+TDF and 3TC+ABV+TDF together with lopinavir/rtv or nevirapine. Subsequently, in a second phase of the study, in the group of patients given ABV and/or 3TC + TDF + lopinavir/rtv, the pharmacokinetic determinations will be repeated after a 4-week interruption of the TDF .
- Conditions
- HIV
- Being tested
- Patients in treatment with 3TC + TDF + LPV/rtv, stop tenofovir during 4 weeks, Patients in treatment with ABV + TDF + LPV/rtv, stop tenofovir during 4 weeks, Patients in treatment with 3TC + ABV + TDF+ LPV/rtv, stop TDF during 4 weeks
- Keywords
- Intracellular concentrations, Plasma concentration, Abacavir, Tenofovir, Lamivudine (3TC), Pharmacokinetic interactions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Patients in treatment with 3TC + TDF + LPV/rtv, stop tenofovir during 4 weeksDrug
Also called Epivir, Kaletra
3TC (300 mg/24 h, 1 tablet/24 h) + Lopinavir/ritonavir (400 mg/12 h, 3 tablets/12 h)
Patients in treatment with ABV + TDF + LPV/rtv, stop tenofovir during 4 weeksDrug
Also called Ziagen, Kaletra
ABV (300 mg/12 h, 1 tablet/12 h)+ Lopinavir/ritonavir (400 mg/12 h, 3 tablets/12 h)
Patients in treatment with 3TC + ABV + TDF+ LPV/rtv, stop TDF during 4 weeksDrug
Also called Epivir, Ziagen, Kaletra
3TC (300 mg/24 h, 1 tablet/24 h)+ ABV (300 mg/12 h, 1 tablet/12 h)+ Lopinavir/ritonavir (400 mg/12 h, 3 tablets/12 h).
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Phase I: 3TC + TDF + NVP or LPV/rtv
Phase II: patients on treatment with LPV/rtv, stop TDF during 4 weeks: 3TC + LPV/rtv Receives: Drug: Patients in treatment with 3TC + TDF + LPV/rtv, stop tenofovir during 4 weeks |
| 2 | Experimental | Phase I: ABV + TDF + NVP or LPV/rtv
Phase II: patients on treatment with LPV/rtv, stop TDF during 4 weeks: ABV + LPV/rtv Receives: Drug: Patients in treatment with ABV + TDF + LPV/rtv, stop tenofovir during 4 weeks |
| 3 | Experimental | Phase I: 3TC + ABV + TDF + NVP or LPV/rtv
Phase II: patients on treatment with LPV/rtv, stop TDF during 4 weeks: 3TC + ABV + LPV/rtv Receives: Drug: Patients in treatment with 3TC + ABV + TDF+ LPV/rtv, stop TDF during 4 weeks |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint will be the variation between the intracellular levels of 3TC and ABC before and after the interruption of the treatment with TDF
Measured: At baseline and week 4.
Secondary outcomes (3)
Variations between the plasma levels of 3TC and ABC before and after interruption of the treatment with TDF.
Measured: at baseline and week 4
Correlation between the intracellular and plasma levels of 3TC, ABC and TDF.
Measured: at baseline and week 4
Changes in the intracellular levels of TDF following the withdrawal of the drug.
Measured: At week 4.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2006 (estimated)
- Study startJan 2005
- Primary completionSep 2005
- Study completionSep 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIVStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Germans Trias i Pujol Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
- Investigators
- Bonaventura Clotet, MD,PhD, Principal investigator, LLuita contra la Sida Foundation-HIV Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00335192
- Sponsor's protocol ID
- INTRANUCS
- Other IDs
- 2004-000948-25, 2004
- Status last verified
- Sep 2008
- First submitted
- 8 Jun 2006
- Last updated
- 8 Sep 2008
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Determination of Plasma and Intracellular Levels of Nucleoside Reverse Transcriptase Inhibitors (NRTI) and of Nucleotide Analog Tenofovir Disoproxil Fumarate (TDF) in Patients Treated With Abacavir and/or Lamivudine Given With or Without TDF.
- ClinicalTrials.gov ID
- NCT00335192
- Acronym / sponsor ID
- INTRANUCS
- Conditions
- HIV
- Keywords
- Intracellular concentrations, Plasma concentration, Abacavir, Tenofovir, Lamivudine (3TC), Pharmacokinetic interactions
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Germans Trias i Pujol HospitalUniversity, hospital or other
- Collaborators
- Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
- Study start
- Jan 2005
- Primary completion
- Sep 2005 (actual)
- Study completion
- Sep 2005 (actual)
- First posted
- 9 Jun 2006 (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 evaluate if there are pharmacokinetic interactions between the NRTI 3TC and ABV, and the TDF nucleotide. For this purpose, the intracellular and plasma levels of 3TC and ABV will be compared in patients given these nucleosides with TDF and 30 days after the interruption of the TDF.
Detailed description
There is clear evidence of pharmacokinetic interaction between ddI+TDF. However, the interaction between TDF and other NRTIs, mainly at intracellular level, has not been so well studied.
Since all the NRTIs are anabolized at intracellular level by numerous kinases, and are transported by passive carrier systems, the interaction may be between TDF and other NRTIs.
This study aims to investigate the pharmacokinetic interactions between the TDF and the nucleosides abacavir (ABV) and lamivudine (3TC) at plasma and intracellular level.
With this objective, intracellular and plasma levels will be analysed in a group of patients that receive the combinations 3TC +TDF, ABV+TDF and 3TC+ABV+TDF together with lopinavir/rtv or nevirapine. Subsequently, in a second phase of the study, in the group of patients given ABV and/or 3TC + TDF + lopinavir/rtv, the pharmacokinetic determinations will be repeated after a 4-week interruption of the TDF .
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Patients in treatment with 3TC + TDF + LPV/rtv, stop tenofovir during 4 weeksPhase I: 3TC + TDF + NVP or LPV/rtv Phase II: patients on treatment with LPV/rtv, stop TDF during 4 weeks: 3TC + LPV/rtv |
| 2 | Experimental | Drug: Patients in treatment with ABV + TDF + LPV/rtv, stop tenofovir during 4 weeksPhase I: ABV + TDF + NVP or LPV/rtv Phase II: patients on treatment with LPV/rtv, stop TDF during 4 weeks: ABV + LPV/rtv |
| 3 | Experimental | Drug: Patients in treatment with 3TC + ABV + TDF+ LPV/rtv, stop TDF during 4 weeksPhase I: 3TC + ABV + TDF + NVP or LPV/rtv Phase II: patients on treatment with LPV/rtv, stop TDF during 4 weeks: 3TC + ABV + LPV/rtv |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- HIV+ patients aged above 18 years.
- Undetectable HIV viral load in the last determination
- Patients capable of correct compliance according to clinical criteria.
- Patients on triple HAART therapy for the previous 3 months including 3TC and/or ABV and TDF, with a PI (Lopinavir/ritonavir) or an NNRTI (Nevirapine)
- Women may not be of fertile age (defined as at least one year from menopause or undergoing any surgical sterilisation technique), or must undertake to use a barrier contraceptive method during the study.
Key exclusion criteria (5 listed)
- Incorrect therapeutic compliance over the four weeks before the beginning of the study.
- Interruption or withdrawal from therapy during follow-up.
- Concomitant treatment with any drug which according to the clinician's criterion may interact with the investigational antiretrovirals, such as other antiretrovirals.
- Triple HAART therapy including Nevirapine (for phase II)
- Documented or suspected resistance to ABV, 3TC or lopinavir/rtv (for phase II).
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 |
|---|---|---|
| Patients in treatment with 3TC + TDF + LPV/rtv, stop tenofovir during 4 weeksAlso: Epivir, Kaletra3TC (300 mg/24 h, 1 tablet/24 h) + Lopinavir/ritonavir (400 mg/12 h, 3 tablets/12 h) | Drug | 1 |
| Patients in treatment with ABV + TDF + LPV/rtv, stop tenofovir during 4 weeksAlso: Ziagen, KaletraABV (300 mg/12 h, 1 tablet/12 h)+ Lopinavir/ritonavir (400 mg/12 h, 3 tablets/12 h) | Drug | 2 |
| Patients in treatment with 3TC + ABV + TDF+ LPV/rtv, stop TDF during 4 weeksAlso: Epivir, Ziagen, Kaletra3TC (300 mg/24 h, 1 tablet/24 h)+ ABV (300 mg/12 h, 1 tablet/12 h)+ Lopinavir/ritonavir (400 mg/12 h, 3 tablets/12 h). | Drug | 3 |
Primary outcome
The primary endpoint will be the variation between the intracellular levels of 3TC and ABC before and after the interruption of the treatment with TDF
Time frame: At baseline and week 4.
3 secondary outcomes
Variations between the plasma levels of 3TC and ABC before and after interruption of the treatment with TDF.
Time frame: at baseline and week 4
Correlation between the intracellular and plasma levels of 3TC, ABC and TDF.
Time frame: at baseline and week 4
Changes in the intracellular levels of TDF following the withdrawal of the drug.
Time frame: At week 4.
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 8 Sep 2008.
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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.
Bonaventura Clotet, MD,PhD principal investigator
LLuita contra la Sida Foundation-HIV Unit
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 Patients in treatment with 3TC + TDF + LPV/rtv, stop tenofovir during 4 weeks, Patients in treatment with ABV + TDF + LPV/rtv, stop tenofovir during 4 weeks and Patients in treatment with 3TC + ABV + TDF+ LPV/rtv, stop TDF during 4 weeks in people with HIV, run by Germans Trias i Pujol Hospital at 1 site in Spain.
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 6 inclusion and 5 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 8 Sep 2008. 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 Spain. 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?
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.
What does the primary outcome measure?
The primary endpoint will be the variation between the intracellular levels of 3TC and ABC before and after the interruption of the treatment with TDF (time frame: At baseline and week 4.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Sep 2008.