To Determine if There Are Pharmacokinetic Interactions at Plasma or Intracellular Level Between Nucleosides and Tenofovir
Information source: Germans Trias i Pujol Hospital
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV
Intervention: 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 (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Germans Trias i Pujol Hospital Official(s) and/or principal investigator(s): Bonaventura Clotet, MD,PhD, Principal Investigator, Affiliation: LLuita contra la Sida Foundation-HIV Unit
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.
Clinical Details
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.
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
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
Secondary outcome: Variations between the plasma levels of 3TC and ABC before and after interruption of the treatment with TDF.Correlation between the intracellular and plasma levels of 3TC, ABC and TDF. Changes in the intracellular levels of TDF following the withdrawal of the drug.
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
Minimum age: 18 Years.
Maximum age: 80 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. HIV+ patients aged above 18 years.
2. Undetectable HIV viral load in the last determination
3. Patients capable of correct compliance according to clinical criteria.
4. 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)
5. 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.
6. Ability to provide informed consent.
Exclusion Criteria:
1. Incorrect therapeutic compliance over the four weeks before the beginning of the
study.
2. Interruption or withdrawal from therapy during follow-up.
3. Concomitant treatment with any drug which according to the clinician's criterion may
interact with the investigational antiretrovirals, such as other antiretrovirals.
4. Triple HAART therapy including Nevirapine (for phase II)
5. Documented or suspected resistance to ABV, 3TC or lopinavir/rtv (for phase II).
Locations and Contacts
Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona 08916, Spain
Additional Information
Starting date: January 2005
Last updated: September 5, 2008
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