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

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ClinicalTrials.gov Identifier: NCT00307502

Recruitment Status : Completed

First Posted : March 28, 2006

Last Update Posted : February 23, 2010

Sponsor:

Collaborator:

Fundacio Lluita Contra la SIDA

Information provided by:

Germans Trias i Pujol Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
HIV Infections	Drug: Nevirapine Drug: Efavirenz Drug: Indinavir/ritonavir Drug: Nelfinavir Drug: Saquinavir/ritonavir Drug: Lopinavir/ritonavir Drug: Atazanavir Drug: Atazanavir/ritonavir Drug: Fos-amprenavir/ritonavir Drug: Tipranavir/ ritonavir Drug: Darunavir/ritonavir	Phase 1

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 Design


Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	675 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Cross-sectional Study for the Characterisation of the Pharmacokinetic Parameters of Protease Inhibitors and Non-nucleoside Analog Reverse Transcriptase Inhibitors in the Spanish Population of HIV-infected Subjects
Study Start Date :	January 2005
Actual Primary Completion Date :	December 2009
Actual Study Completion Date :	December 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: NVP Nevirapine	Drug: Nevirapine tablets 200 mg, 400 mg/day Other Name: Viramune
Experimental: EFV Efavirenz	Drug: Efavirenz tablets 600 mg, 600 mg/day Other Name: Sustiva
Experimental: INV Indinavir/ritonavir	Drug: Indinavir/ritonavir Indinavir: capsules 400 mg, 1600 mg/day Ritonavir: capsules 100 mg, 200 mg/day Other Name: Crixivan/norvir
Experimental: NFV Nelfinavir	Drug: Nelfinavir tablets 250 mg, 2500 mg/day Other Name: Viracept
Experimental: SQV Saquinavir/ritonavir	Drug: Saquinavir/ritonavir Saquinavir: tablets 500 mg, 2000 mg/day Ritonavir: tablets 100 mg, 200 mg/day Other Name: Invirase/Norvir
Experimental: LPV Lopinavir/ritonavir	Drug: Lopinavir/ritonavir tablets lopinavir 200 mg + ritonavir 50 mg, 800/200 mg/day Other Name: Kaletra
Experimental: ATV Atazanavir	Drug: Atazanavir capsules 200 mg, 400 mg/day Other Name: Reyataz
Experimental: ATV/rtv Atazanavir/ritonavir	Drug: Atazanavir/ritonavir Atazanavir: capsules 150 mg, 300 mg/day Ritonavir: capsules 100 mg, 200 mg/day Other Name: Reyataz/Norvir
Experimental: Fos-APV Fos-amprenavir/ritonavir	Drug: Fos-amprenavir/ritonavir Fos-amprenavir: capsules 700 mg, 1400 mg/day Ritonavir: capsules 100 mg, 200 mg/day Other Name: Telzir/norvir
Experimental: TPV Tipranavir/ritonavir	Drug: Tipranavir/ ritonavir Tipranavir: tablets 250 mg, 1000 mg/day Ritonavir: capsules 100 mg, 400 mg/day Other Name: Aptivus/Norvir
Experimental: DRV Darunavir/ritonavir	Drug: Darunavir/ritonavir Darunavir: tablets 300 mg, 1200 mg/day Ritonavir: capsules 100 mg, 200 mg/day Other Name: Prezista/norvir

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

Demographic: race, gender, age [ Time Frame: In the 12 h pharmacokinetic curve ]
Clinical: weight, height, liver/renal impairment, HIV infection stage, tobacco/alcohol consumption [ Time Frame: In the 12 h pharmacokinetic curve ]
Adverse events [ Time Frame: 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 [ Time Frame: In the 12 h pharmacokinetic curve ]
Antiretroviral and concomitant treatment, adherence (number of doses omitted in the last two weeks) [ Time Frame: 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) [ Time Frame: In the 12 h pharmacokinetic curve ]
Genetic study of polymorphism of CYP3A4 and P-glycoprotein [ Time Frame: In the 12 h pharmacokinetic curve ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age higher than 18 years.
Documented HIV infection (at least one positive Western-blot)
Stable antiretroviral treatment with PI or NNRTI, no changes over the last 4 weeks.
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:

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).
Treatment with other drugs with known significant pharmacological interactions with the investigational drug over the previous two weeks.
Unsuitable adherence to treatment (one or more doses omitted in the last week, or two or more doses omitted in the last two weeks).
Presence of clinical findings or a background of gastrointestinal disease or digestive surgery that may interfere in the pharmacokinetics of the medication.
Active consumption of alcohol (>50 grams/day) or illegal drugs (except cannabis).
In the case of women, pregnancy or breastfeeding.
Record or suspicion of inability to cooperate properly

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00307502

Locations


Spain
Germans Trias i Pujol Hospital
Badalona, Barcelona, Spain, 08916
Hospital de Figueres
Figueras, Barcelona, Spain, 17600
Fundació Hospital-Asil de Granollers
Granollers, Barcelona, Spain, 08400
Hospital de Vic
Vic, Barcelona, Spain, 08500
Hospital Universitari Sant Joan de Reus
Reus, Tarragona, Spain, 43201
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08025

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Moltó J, Xinarianos G, Miranda C, Pushpakom S, Cedeño S, Clotet B, Owen A, Valle M. Simultaneous pharmacogenetics-based population pharmacokinetic analysis of darunavir and ritonavir in HIV-infected patients. Clin Pharmacokinet. 2013 Jul;52(7):543-53. doi: 10.1007/s40262-013-0057-6.


Responsible Party:	Lluita Sida Foundation
ClinicalTrials.gov Identifier:	NCT00307502 History of Changes
Other Study ID Numbers:	PK-TRANSVERSAL 2004-001516-32
First Posted:	March 28, 2006 Key Record Dates
Last Update Posted:	February 23, 2010
Last Verified:	February 2010

Keywords provided by Germans Trias i Pujol Hospital:


protease inhibitors non-nucleoside analog reverse transcriptase inhibitors pharmacokinetic models treatment experienced HIV

Additional relevant MeSH terms:


HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Ritonavir Lopinavir Darunavir Atazanavir Sulfate HIV Protease Inhibitors Nelfinavir	Indinavir Saquinavir Amprenavir Fosamprenavir Nevirapine Tipranavir Efavirenz Protease Inhibitors Reverse Transcriptase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents

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