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

NCT ID: NCT00335192

Last Updated: 2008-09-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-01-31
• Study Completion Date: 2005-09-30

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.

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 .

Conditions

HIV

Keywords

Intracellular concentrations; Plasma concentration; Abacavir; Tenofovir; Lamivudine (3TC); Pharmacokinetic interactions

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

3TC (300 mg/24 h, 1 tablet/24 h) + Lopinavir/ritonavir (400 mg/12 h, 3 tablets/12 h)

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

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

ABV (300 mg/12 h, 1 tablet/12 h)+ Lopinavir/ritonavir (400 mg/12 h, 3 tablets/12 h)

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

Group Type: EXPERIMENTAL

Patients in treatment with 3TC + ABV + TDF+ LPV/rtv, stop TDF during 4 weeks

Intervention Type: DRUG

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).

Interventions

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)

Intervention Type: 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)

Intervention Type: 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).

Intervention Type: DRUG

Other Intervention Names

Epivir; Kaletra; Ziagen; Kaletra; Epivir; Ziagen; Kaletra

Eligibility 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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

OTHER

Sponsor Role: collaborator

Germans Trias i Pujol Hospital

OTHER

Sponsor Role: lead

Responsible Party

LLuita Sida Foundation

Principal Investigators

Bonaventura Clotet, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

LLuita contra la Sida Foundation-HIV Unit

Locations

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, Spain

Countries

Spain

Other Identifiers

2004-000948-25

Identifier Type: -

Identifier Source: secondary_id

INTRANUCS

Identifier Type: -

Identifier Source: org_study_id