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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:
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

June 8, 2006
September 5, 2008
January 2005
September 2005   (final data collection date for 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. ] [ Designated as safety issue: No ]
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
Complete list of historical versions of study NCT00335192 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: No ]
  • Correlation between the intracellular and plasma levels of 3TC, ABC and TDF. [ Time Frame: at baseline and week 4 ] [ Designated as safety issue: No ]
  • Changes in the intracellular levels of TDF following the withdrawal of the drug. [ Time Frame: At week 4. ] [ Designated as safety issue: No ]
  • 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 3HT, ABC and TDF.
  • Changes in the intracellular levels of TDF following the withdrawal of the drug.
Not Provided
Not Provided
 
To Determine if There Are Pharmacokinetic Interactions at Plasma or Intracellular Level Between Nucleosides and Tenofovir
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.

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 .

Interventional
Phase 4
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV
  • 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:
    • Epivir
    • Kaletra
  • 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:
    • Ziagen
    • Kaletra
  • 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:
    • Epivir
    • Ziagen
    • Kaletra
  • 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

    Intervention: Drug: Patients in treatment with 3TC + TDF + LPV/rtv, stop tenofovir during 4 weeks
  • 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

    Intervention: Drug: Patients in treatment with ABV + TDF + LPV/rtv, stop tenofovir during 4 weeks
  • 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

    Intervention: Drug: Patients in treatment with 3TC + ABV + TDF+ LPV/rtv, stop TDF during 4 weeks
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
32
September 2005
September 2005   (final data collection date for primary outcome measure)

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).
Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
Spain
 
NCT00335192
INTRANUCS, 2004-000948-25
No
LLuita Sida Foundation
Germans Trias i Pujol Hospital
Fundacio Lluita Contra la SIDA
Principal Investigator: Bonaventura Clotet, MD,PhD LLuita contra la Sida Foundation-HIV Unit
Germans Trias i Pujol Hospital
September 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP