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To Determine if There Are Pharmacokinetic Interactions at Plasma or Intracellular Level Between Nucleosides and Tenofovir

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ClinicalTrials.gov Identifier: NCT00335192
Recruitment Status : Completed
First Posted : June 9, 2006
Last Update Posted : September 8, 2008
Sponsor:
Collaborator:
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
Information provided by:
Germans Trias i Pujol Hospital

Study Description
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Brief 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.

Condition or disease Intervention/treatment 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

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
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (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.
Study Start Date : January 2005
Actual Primary Completion Date : September 2005
Actual Study Completion Date : September 2005

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arms and Interventions
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Arm Intervention/treatment
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:
  • Epivir
  • Kaletra
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:
  • Ziagen
  • Kaletra
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:
  • Epivir
  • Ziagen
  • Kaletra


Outcome Measures
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Primary Outcome Measures :
  1. 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 :
  1. 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 ]
  2. Correlation between the intracellular and plasma levels of 3TC, ABC and TDF. [ Time Frame: at baseline and week 4 ]
  3. Changes in the intracellular levels of TDF following the withdrawal of the drug. [ Time Frame: At week 4. ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00335192


Locations
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Spain
Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, Spain, 08916
Sponsors and Collaborators
Germans Trias i Pujol Hospital
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
Investigators
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Principal Investigator: Bonaventura Clotet, MD,PhD LLuita contra la Sida Foundation-HIV Unit
More Information
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Responsible Party: LLuita Sida Foundation
ClinicalTrials.gov Identifier: NCT00335192    
Other Study ID Numbers: INTRANUCS
2004-000948-25
First Posted: June 9, 2006    Key Record Dates
Last Update Posted: September 8, 2008
Last Verified: September 2008
Keywords provided by Germans Trias i Pujol Hospital:
Intracellular concentrations
Plasma concentration
Abacavir
 Tenofovir
Lamivudine (3TC)
Pharmacokinetic interactions
Additional relevant MeSH terms:
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Tenofovir
Lamivudine
Lopinavir
Abacavir
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
 Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
HIV Protease Inhibitors
Protease Inhibitors
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors