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

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:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Lamivudine Abacavir Tenofovir Abacavir sulfate Lopinavir Tenofovir Disoproxil Fumarate

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 (Adult, Senior)
Genders Eligible for Study:	Both
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

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


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:


Lamivudine Tenofovir Reverse Transcriptase Inhibitors Abacavir 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 September 27, 2016