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

Phase 1

Completed

• Conditions: HIV Infections
• Interventions: Drug: Nelfinavir; Drug: Saquinavir/ritonavir; Drug: Lopinavir/ritonavir; Drug: Atazanavir; Drug: Atazanavir/ritonavir; Drug: Fos-amprenavir/ritonavir; Drug: Tipranavir/ ritonavir; Drug: Darunavir/ritonavir; Drug: Nevirapine; Drug: Efavirenz; Drug: Indinavir/ritonavir

• Registration Number: NCT00307502
• Lead Sponsor: Germans Trias i Pujol Hospital

Brief Summary

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.

Detailed 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.

Study Timeline

• Study Start: 2005-01
• Study First Submitted: 2006-03-27
• Study First Submitted QC: 2006-03-27
• Study First Posted: 2006-03-28
• Primary Completion: 2009-12
• Study Completion: 2009-12
• Status Verified: 2019-12
• Last Update Submitted: 2019-12-03
• Last Update Posted: 2019-12-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 675

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
NFV	Nelfinavir	Nelfinavir
SQV	Saquinavir/ritonavir	Saquinavir/ritonavir
LPV	Lopinavir/ritonavir	Lopinavir/ritonavir
ATV	Atazanavir	Atazanavir
ATV/rtv	Atazanavir/ritonavir	Atazanavir/ritonavir
Fos-APV	Fos-amprenavir/ritonavir	Fos-amprenavir/ritonavir
TPV	Tipranavir/ ritonavir	Tipranavir/ritonavir
DRV	Darunavir/ritonavir	Darunavir/ritonavir
NVP	Nevirapine	Nevirapine
EFV	Efavirenz	Efavirenz
INV	Indinavir/ritonavir	Indinavir/ritonavir

Primary Outcome Measures

Name	Time	Method
The primary endpoint is the plasma concentration of the PI/NNRTI drugs (Ka absorption constant, CI: plasma clearance, Vd: volume of distribution).	In the 12 hour (h) pharmacokinetic curve

Secondary Outcome Measures

Name	Time	Method
Demographic: race, gender, age	In the 12 h pharmacokinetic curve
Adverse events	In the 12 h pharmacokinetic curve
Clinical: weight, height, liver/renal impairment, HIV infection stage, tobacco/alcohol consumption	In the 12 h pharmacokinetic curve
Laboratory: creatinine, albumin, Quick Index, bilirubin, GOT, GPT, GGT, FA, CD4 lymphocyte count, HIV viral load, HBsAg and anti-HCV, alpha acid glycoprotein	In the 12 h pharmacokinetic curve
Antiretroviral and concomitant treatment, adherence (number of doses omitted in the last two weeks)	In the 12 h pharmacokinetic curve
Pharmacokinetics: maximum concentration (Cmax), time to maximum concentration (Tmax), plasma concentration at the end of the posology interval (Ctrough), half-life (T1/2), area under the curve (ABC)	In the 12 h pharmacokinetic curve
Genetic study of polymorphism of CYP3A4 and P-glycoprotein	In the 12 h pharmacokinetic curve

Trial Locations

Locations (6)

Hospital de Figueres; 🇪🇸 Figueras, Barcelona, Spain

Hospital Universitari Sant Joan de Reus; 🇪🇸 Reus, Tarragona, Spain

Germans Trias i Pujol Hospital; 🇪🇸 Badalona, Barcelona, Spain

Hospital de la Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain

Fundació Hospital-Asil de Granollers; 🇪🇸 Granollers, Barcelona, Spain

Hospital de Vic; 🇪🇸 Vic, Barcelona, Spain