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

HIV Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00335192
• Other study ID #: INTRANUCS
• Secondary ID: 2004-000948-25
• Status: Completed
• Phase: Phase 4
• First received: June 8, 2006
• Last updated: September 5, 2008
• Start date: January 2005
• Est. completion date: September 2005

Study information

• Verified date: September 2008
• Source: Germans Trias i Pujol Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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 .

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: September 2005
• Est. primary completion date: September 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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).

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV

Intervention

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)
• 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)
• 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).

Locations

Country	Name	City	State
Spain	Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
Germans Trias i Pujol Hospital	Fundacio Lluita Contra la SIDA

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		At baseline and week 4.	No
Secondary	Variations between the plasma levels of 3TC and ABC before and after interruption of the treatment with TDF.		at baseline and week 4	No
Secondary	Correlation between the intracellular and plasma levels of 3TC, ABC and TDF.		at baseline and week 4	No
Secondary	Changes in the intracellular levels of TDF following the withdrawal of the drug.		At week 4.	No