Study to Determine the Pharmacokinetic Behavior of Antiretroviral Drugs in Patients Infected by HIV

Germans Trias i Pujol Hospital

Status and phase: Completed; Phase 1

Conditions: HIV Infections

Treatments: Drug: Efavirenz; Drug: Tipranavir/ ritonavir; Drug: Nevirapine; Drug: Saquinavir/ritonavir; Drug: Atazanavir/ritonavir; Drug: Fos-amprenavir/ritonavir; Drug: Nelfinavir; Drug: Darunavir/ritonavir; Drug: Atazanavir; Drug: Lopinavir/ritonavir; Drug: Indinavir/ritonavir

Study type: Interventional

Funder types: Other

Identifiers

NCT00307502

2004-001516-32

PK-TRANSVERSAL

Details and patient eligibility

About

The purpose of this study is to characterise the pharmacokinetic profiles of non-nucleoside analog reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs), and the influence of the individual characteristics on the pharmacokinetic parameters in the Spanish population of HIV-infected subjects.

Full description

The antiretrovirals were administered conventionally according to fixed dosage systems, or depending on the weight of the individual in the case of certain agents. However, the plasma levels of antiretrovirals following the administration of a fixed dose present a marked interindividual variability. Moreover, a significant proportion of the patients on treatment with PIs presented plasma levels regarded as suboptimal in previous studies.

Moreover, for the correct modification of the dosage of a drug, populational data on its pharmacokinetic behaviour during the dosing interval is required. Only by integrating this information with the specific characteristics of each individual is it possible, using mathematical models, to estimate the effect that a modification of the dosage of the drug would have on its plasma concentration. However, populational data on the pharmacokinetic behaviour of antiretroviral agents are still very limited at this moment, and have not always been obtained in populations similar to the one to which they are to be applied.

Thus, knowing the pharmacokinetic behaviour of the antiretroviral agents in our population and the influence of certain individual characteristics on this behaviour may be of great interest, since only in this way will we be able to tailor the dosage of antiretrovirals reliably in our patients.

Enrollment: 675 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age higher than 18 years.
2. Documented HIV infection (at least one positive Western-blot)
3. Stable antiretroviral treatment with PI or NNRTI, no changes over the last 4 weeks.
4. Women may not be of fertile age (defined as at least one year from menopause or undergoing any surgical sterilisation technique), or negative pregnancy test.

Exclusion criteria

1. Subjects on treatment with more than one PI or with combinations of PI and NNRTI (the use of ritonavir in doses below 400 mg BID will not be regarded as a second PI).
2. Treatment with other drugs with known significant pharmacological interactions with the investigational drug over the previous two weeks.
3. Unsuitable adherence to treatment (one or more doses omitted in the last week, or two or more doses omitted in the last two weeks).
4. Presence of clinical findings or a background of gastrointestinal disease or digestive surgery that may interfere in the pharmacokinetics of the medication.
5. Active consumption of alcohol (>50 grams/day) or illegal drugs (except cannabis).
6. In the case of women, pregnancy or breastfeeding.
7. Record or suspicion of inability to cooperate properly

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

675 participants in 11 patient groups

NVP

Experimental group

Description:

Nevirapine

Treatment:

Drug: Nevirapine

EFV

Experimental group

Description:

Efavirenz

Treatment:

Drug: Efavirenz

INV

Experimental group

Description:

Indinavir/ritonavir

Treatment:

Drug: Indinavir/ritonavir

NFV

Experimental group

Description:

Nelfinavir

Treatment:

Drug: Nelfinavir

SQV

Experimental group

Description:

Saquinavir/ritonavir

Treatment:

Drug: Saquinavir/ritonavir

LPV

Experimental group

Description:

Lopinavir/ritonavir

Treatment:

Drug: Lopinavir/ritonavir

ATV

Experimental group

Description:

Atazanavir

Treatment:

Drug: Atazanavir

ATV/rtv

Experimental group

Description:

Atazanavir/ritonavir

Treatment:

Drug: Atazanavir/ritonavir

Fos-APV

Experimental group

Description:

Fos-amprenavir/ritonavir

Treatment:

Drug: Fos-amprenavir/ritonavir

TPV

Experimental group

Description:

Tipranavir/ritonavir

Treatment:

Drug: Tipranavir/ ritonavir

DRV

Experimental group

Description:

Darunavir/ritonavir

Treatment:

Drug: Darunavir/ritonavir