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To Determine if There Are Pharmacokinetic Interactions at Plasma or Intracellular Level Between Nucleosides and Tenofovir
This study has been completed.
Sponsor:
Germans Trias i Pujol Hospital
Collaborator:
Fundacio Lluita Contra la SIDA
Information provided by:
Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier:
NCT00335192
First received: June 8, 2006
Last updated: September 5, 2008
Last verified: September 2008
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
| HIV | Drug: Patients in treatment with 3TC + TDF + LPV/rtv, stop tenofovir during 4 weeks Drug: Patients in treatment with ABV + TDF + LPV/rtv, stop tenofovir during 4 weeks Drug: Patients in treatment with 3TC + ABV + TDF+ LPV/rtv, stop TDF during 4 weeks | Phase 4 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment |
| 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. |
Resource links provided by NLM:
Further study details as provided by Germans Trias i Pujol Hospital:
Primary Outcome Measures:
- 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. ]
Secondary Outcome Measures:
- 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. ]
| Enrollment: | 32 |
| Study Start Date: | January 2005 |
| Study Completion Date: | September 2005 |
| Primary Completion Date: | September 2005 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 1
Phase I: 3TC + TDF + NVP or LPV/rtv Phase II: patients on treatment with LPV/rtv, stop TDF during 4 weeks: 3TC + LPV/rtv |
Drug: Patients in treatment with 3TC + TDF + LPV/rtv, stop tenofovir during 4 weeks
3TC (300 mg/24 h, 1 tablet/24 h) + Lopinavir/ritonavir (400 mg/12 h, 3 tablets/12 h)
Other Names:
|
|
Experimental: 2
Phase I: ABV + TDF + NVP or LPV/rtv Phase II: patients on treatment with LPV/rtv, stop TDF during 4 weeks: ABV + LPV/rtv |
Drug: Patients in treatment with ABV + TDF + LPV/rtv, stop tenofovir during 4 weeks
ABV (300 mg/12 h, 1 tablet/12 h)+ Lopinavir/ritonavir (400 mg/12 h, 3 tablets/12 h)
Other Names:
|
|
Experimental: 3
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 |
Drug: Patients in treatment with 3TC + ABV + TDF+ LPV/rtv, stop TDF during 4 weeks
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).
Other Names:
|
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 .
Eligibility| Ages Eligible for Study: | 18 Years to 80 Years (Adult, Senior) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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).
Contacts and Locations
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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00335192
Please refer to this study by its ClinicalTrials.gov identifier: NCT00335192
Locations
| Spain | |
| Hospital Universitari Germans Trias i Pujol | |
| Badalona, Barcelona, Spain, 08916 | |
Sponsors and Collaborators
Germans Trias i Pujol Hospital
Fundacio Lluita Contra la SIDA
Investigators
| Principal Investigator: | Bonaventura Clotet, MD,PhD | LLuita contra la Sida Foundation-HIV Unit |
More Information
| Responsible Party: | LLuita Sida Foundation |
| ClinicalTrials.gov Identifier: | NCT00335192 History of Changes |
| Other Study ID Numbers: |
INTRANUCS 2004-000948-25 |
| Study First Received: | June 8, 2006 |
| Last Updated: | September 5, 2008 |
Keywords provided by Germans Trias i Pujol Hospital:
|
Intracellular concentrations Plasma concentration Abacavir |
Tenofovir Lamivudine (3TC) Pharmacokinetic interactions |
Additional relevant MeSH terms:
|
Lamivudine Tenofovir Abacavir Reverse Transcriptase Inhibitors Lopinavir Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Anti-HIV Agents HIV Protease Inhibitors Protease Inhibitors Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors |
ClinicalTrials.gov processed this record on June 28, 2017