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

This study has been completed.
Sponsor:
Collaborator:
Fundacio Lluita Contra la SIDA
Information provided by:
Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier:
NCT00307502
First received: March 27, 2006
Last updated: February 22, 2010
Last verified: February 2010
  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 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: 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

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
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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:

  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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

No publications provided by Germans Trias i Pujol Hospital

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Lluita Sida Foundation
ClinicalTrials.gov Identifier: NCT00307502     History of Changes
Other Study ID Numbers: PK-TRANSVERSAL, 2004-001516-32
Study First Received: March 27, 2006
Last Updated: February 22, 2010
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

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Protease Inhibitors
Indinavir
Saquinavir
Ritonavir
Nelfinavir
Amprenavir
Lopinavir
Atazanavir
Fosamprenavir
Darunavir
HIV Protease Inhibitors
Nevirapine
Reverse Transcriptase Inhibitors
Efavirenz
Tipranavir
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 14, 2014