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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

March 27, 2006
February 22, 2010
January 2005
December 2009   (final data collection date for primary outcome measure)
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 ]
  • Vd: volume of distribution
  • The primary endpoint is the plasma concentration of the PI/NNRTI drugs. Assuming a mono-compartmental pharmacokinetic model with first-order kinetics, the following pharmacokinetic parameters will be estimated for each study group:
  • Ka: absorption constant
  • Cl: plasma clearance
Complete list of historical versions of study NCT00307502 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Demographic: race, gender, age.
  • Clinical: weight, height, liver/renal impairment, HIV infection stage, tobacco/alcohol consumption.
  • Adverse events
  • Laboratory: creatinine, albumin, Quick Index, bilirubin, GOT, GPT, GGT, FA, CD4 lymphocyte count, HIV viral load, HBsAg and anti-HCV.
  • Antiretroviral and concomitant treatment, adherence (number of doses omitted in the last two weeks).
  • 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).
Not Provided
Not Provided
 
Study to Determine the Pharmacokinetic Behavior of Antiretroviral Drugs in Patients Infected by HIV
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

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.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV Infections
  • Drug: Nevirapine
    tablets 200 mg, 400 mg/day
    Other Name: Viramune
  • Drug: Efavirenz
    tablets 600 mg, 600 mg/day
    Other Name: Sustiva
  • Drug: Indinavir/ritonavir

    Indinavir: capsules 400 mg, 1600 mg/day

    Ritonavir: capsules 100 mg, 200 mg/day

    Other Name: Crixivan/norvir
  • Drug: Nelfinavir
    tablets 250 mg, 2500 mg/day
    Other Name: Viracept
  • Drug: Saquinavir/ritonavir

    Saquinavir: tablets 500 mg, 2000 mg/day

    Ritonavir: tablets 100 mg, 200 mg/day

    Other Name: Invirase/Norvir
  • Drug: Lopinavir/ritonavir
    tablets lopinavir 200 mg + ritonavir 50 mg, 800/200 mg/day
    Other Name: Kaletra
  • Drug: Atazanavir
    capsules 200 mg, 400 mg/day
    Other Name: Reyataz
  • Drug: Atazanavir/ritonavir

    Atazanavir: capsules 150 mg, 300 mg/day

    Ritonavir: capsules 100 mg, 200 mg/day

    Other Name: Reyataz/Norvir
  • Drug: Fos-amprenavir/ritonavir

    Fos-amprenavir: capsules 700 mg, 1400 mg/day

    Ritonavir: capsules 100 mg, 200 mg/day

    Other Name: Telzir/norvir
  • Drug: Tipranavir/ ritonavir

    Tipranavir: tablets 250 mg, 1000 mg/day

    Ritonavir: capsules 100 mg, 400 mg/day

    Other Name: Aptivus/Norvir
  • Drug: Darunavir/ritonavir

    Darunavir: tablets 300 mg, 1200 mg/day

    Ritonavir: capsules 100 mg, 200 mg/day

    Other Name: Prezista/norvir
  • Experimental: NVP
    Nevirapine
    Intervention: Drug: Nevirapine
  • Experimental: EFV
    Efavirenz
    Intervention: Drug: Efavirenz
  • Experimental: INV
    Indinavir/ritonavir
    Intervention: Drug: Indinavir/ritonavir
  • Experimental: NFV
    Nelfinavir
    Intervention: Drug: Nelfinavir
  • Experimental: SQV
    Saquinavir/ritonavir
    Intervention: Drug: Saquinavir/ritonavir
  • Experimental: LPV
    Lopinavir/ritonavir
    Intervention: Drug: Lopinavir/ritonavir
  • Experimental: ATV
    Atazanavir
    Intervention: Drug: Atazanavir
  • Experimental: ATV/rtv
    Atazanavir/ritonavir
    Intervention: Drug: Atazanavir/ritonavir
  • Experimental: Fos-APV
    Fos-amprenavir/ritonavir
    Intervention: Drug: Fos-amprenavir/ritonavir
  • Experimental: TPV
    Tipranavir/ritonavir
    Intervention: Drug: Tipranavir/ ritonavir
  • Experimental: DRV
    Darunavir/ritonavir
    Intervention: Drug: Darunavir/ritonavir
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
675
December 2009
December 2009   (final data collection date for primary outcome measure)

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
Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
Spain
 
NCT00307502
PK-TRANSVERSAL, 2004-001516-32
No
Lluita Sida Foundation
Germans Trias i Pujol Hospital
Fundacio Lluita Contra la SIDA
Principal Investigator: Bonaventura Clotet, MD, PhD Lluita contra la Sida Foundation-HIV Unit
Germans Trias i Pujol Hospital
February 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP