Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials
Text Size

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
History of Changes
  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
Endpoint Classification: Safety Study
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:

U.S. FDA Resources

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. ] [ Designated as safety issue: No ]

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 ] [ 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 ]
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:
  • 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

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
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

No publications provided

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
Health Authority: Spain: Ministry of Health

Keywords provided by Germans Trias i Pujol Hospital:
Intracellular concentrations
Plasma concentration
Abacavir
 Tenofovir
Lamivudine (3TC)
Pharmacokinetic interactions

Additional relevant MeSH terms:
Tenofovir
Tenofovir disoproxil
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
 Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on February 27, 2015