Study to Determine the Pharmacokinetic Behavior of Antiretroviral Drugs in Patients Infected by HIV - Full Text View

Sponsors and Collaborators:	Germans Trias i Pujol Hospital FUNDACIÓ LLUITA CONTRA LA SIDA
Information provided by:	Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier:	NCT00307502

Purpose

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	Intervention	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 I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Pharmacokinetics Study
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

Resource links provided by NLM:

Further study details as provided by Germans Trias i Pujol Hospital:

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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Demographic: race, gender, age [ Time Frame: In the 12 h pharmacokinetic curve ] [ Designated as safety issue: No ]
Clinical: weight, height, liver/renal impairment, HIV infection stage, tobacco/alcohol consumption [ Time Frame: In the 12 h pharmacokinetic curve ] [ Designated as safety issue: No ]
Adverse events [ Time Frame: In the 12 h pharmacokinetic curve ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
Antiretroviral and concomitant treatment, adherence (number of doses omitted in the last two weeks) [ Time Frame: In the 12 h pharmacokinetic curve ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Genetic study of polymorphism of CYP3A4 and P-glycoprotein [ Time Frame: In the 12 h pharmacokinetic curve ] [ Designated as safety issue: No ]

Estimated Enrollment:	675
Study Start Date:	January 2005
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
NVP: Experimental Nevirapine	Drug: Nevirapine tablets 200 mg, 400 mg/day
EFV: Experimental Efavirenz	Drug: Efavirenz tablets 600 mg, 600 mg/day
INV: Experimental Indinavir/ritonavir	Drug: Indinavir/ritonavir Indinavir: capsules 400 mg, 1600 mg/day Ritonavir: capsules 100 mg, 200 mg/day
NFV: Experimental Nelfinavir	Drug: Nelfinavir tablets 250 mg, 2500 mg/day
SQV: Experimental Saquinavir/ritonavir	Drug: Saquinavir/ritonavir Saquinavir: tablets 500 mg, 2000 mg/day Ritonavir: tablets 100 mg, 200 mg/day
LPV: Experimental Lopinavir/ritonavir	Drug: Lopinavir/ritonavir tablets lopinavir 200 mg + ritonavir 50 mg, 800/200 mg/day
ATV: Experimental Atazanavir	Drug: Atazanavir capsules 200 mg, 400 mg/day
ATV/rtv: Experimental Atazanavir/ritonavir	Drug: Atazanavir/ritonavir Atazanavir: capsules 150 mg, 300 mg/day Ritonavir: capsules 100 mg, 200 mg/day
Fos-APV: Experimental Fos-amprenavir/ritonavir	Drug: Fos-amprenavir/ritonavir Fos-amprenavir: capsules 700 mg, 1400 mg/day Ritonavir: capsules 100 mg, 200 mg/day
TPV: Experimental Tipranavir/ritonavir	Drug: Tipranavir/ ritonavir Tipranavir: tablets 250 mg, 1000 mg/day Ritonavir: capsules 100 mg, 400 mg/day
DRV: Experimental Darunavir/ritonavir	Drug: Darunavir/ritonavir Darunavir: tablets 300 mg, 1200 mg/day Ritonavir: capsules 100 mg, 200 mg/day

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.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00307502

Contacts

Contact: José Moltó, MD

34-93-4978849

jmolto@flsida.org

Locations

Spain
Hospital de la Santa Creu i Sant Pau	Recruiting
Barcelona, Spain, 08025
Principal Investigator: Pere Domingo, MD, PhD
Spain, Barcelona
Germans Trias i Pujol Hospital	Recruiting
Badalona, Barcelona, Spain, 08916
Principal Investigator: Bonaventura Clotet, MD, PhD
Sub-Investigator: José Moltó, MD, PhD
Sub-Investigator: Asunción Blanco, MD
Sub-Investigator: Samandhy Sedeño, MD, PhD
Fundació Hospital-Asil de Granollers	Recruiting
Granollers, Barcelona, Spain, 08400
Principal Investigator: Enric Pedrol, MD, PhD
Hospital de Vic	Recruiting
Vic, Barcelona, Spain, 08500
Principal Investigator: Josep Vilaró, MD, PhD
Hospital de Figueres	Recruiting
Figueras, Barcelona, Spain, 17600
Principal Investigator: Josep Cucurull, MD, PhD
Spain, Tarragona
Hospital Universitari Sant Joan de Reus	Terminated
Reus, Tarragona, Spain, 43201

Sponsors and Collaborators

Germans Trias i Pujol Hospital

FUNDACIÓ LLUITA CONTRA LA SIDA

Investigators

Principal Investigator:

Bonaventura Clotet, MD, PhD

Lluita contra la Sida Foundation-HIV Unit

More Information

No publications provided

Responsible Party:	Lluita Sida Foundation ( Lluita Sida Foundation )
Study ID Numbers:	PK-TRANSVERSAL, 2004-001516-32
Study First Received:	March 27, 2006
Last Updated:	April 8, 2009
ClinicalTrials.gov Identifier:	NCT00307502 History of Changes
Health Authority:	Spain: Ministry of Health

Keywords provided by Germans Trias i Pujol Hospital:

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

Study placed in the following topic categories:

Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Indinavir
Saquinavir
Darunavir
Reverse Transcriptase Inhibitors
Tipranavir
Anti-Bacterial Agents
Amprenavir
Lopinavir
Anti-Retroviral Agents
Nelfinavir
Retroviridae Infections
Efavirenz

HIV Protease Inhibitors
Anti-HIV Agents
Acquired Immunodeficiency Syndrome
Atazanavir
Antiviral Agents
Immunologic Deficiency Syndromes
Protease Inhibitors
Virus Diseases
Nevirapine
Fosamprenavir
Ritonavir
HIV Infections
Sexually Transmitted Diseases
Antitubercular Agents

Additional relevant MeSH terms:

Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Indinavir
Saquinavir
Infection
Darunavir
Tipranavir
Reverse Transcriptase Inhibitors
Anti-Bacterial Agents
Amprenavir
Anti-Retroviral Agents
Lopinavir
Therapeutic Uses

Nelfinavir
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors
HIV Protease Inhibitors
RNA Virus Infections
Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Atazanavir
Antiviral Agents
Pharmacologic Actions
Immunologic Deficiency Syndromes
Antibiotics, Antitubercular
Protease Inhibitors

ClinicalTrials.gov processed this record on September 11, 2009