Clinical trial NCT00307502: Study to Determine the Pharmacokinetic Behavior of Antiretroviral Drugs in Patients Infected by HIV
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: protease inhibitors
non-nucleoside analog reverse transcriptase inhibitors
pharmacokinetic models
treatment experienced
HIV
Lead sponsor: Germans Trias i Pujol Hospital
Sponsor class: OTHER
Collaborators: name: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
First posted: 2006-03-28
Enrollment: 675
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: The primary endpoint is the plasma concentration of the PI/NNRTI drugs (Ka absorption constant, CI: plasma clearance, Vd: volume of distribution).
timeFrame: In the 12 hour (h) pharmacokinetic curve
Secondary outcomes:
measure: Demographic: race, gender, age
timeFrame: In the 12 h pharmacokinetic curve
measure: Clinical: weight, height, liver/renal impairment, HIV infection stage, tobacco/alcohol consumption
timeFrame: In the 12 h pharmacokinetic curve
measure: Adverse events
timeFrame: In the 12 h pharmacokinetic curve
measure: Laboratory: creatinine, albumin, Quick Index, bilirubin, GOT, GPT, GGT, FA, CD4 lymphocyte count, HIV viral load, HBsAg and anti-HCV, alpha acid glycoprotein
timeFrame: In the 12 h pharmacokinetic curve
measure: Antiretroviral and concomitant treatment, adherence (number of doses omitted in the last two weeks)
timeFrame: In the 12 h pharmacokinetic curve
measure: 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)
timeFrame: In the 12 h pharmacokinetic curve
measure: Genetic study of polymorphism of CYP3A4 and P-glycoprotein
timeFrame: In the 12 h pharmacokinetic curve
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Germans Trias i Pujol Hospital
state: Barcelona
city: Figueras
country: Spain
facility: Hospital de Figueres
state: Barcelona
city: Granollers
country: Spain
facility: Fundació Hospital-Asil de Granollers
state: Barcelona
city: Vic
country: Spain
facility: Hospital de Vic
state: Barcelona
city: Reus
country: Spain
facility: Hospital Universitari Sant Joan de Reus
state: Tarragona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
Study officials:
affiliation: Lluita contra la Sida Foundation-HIV Unit
name: Bonaventura Clotet, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Molto J, Xinarianos G, Miranda C, Pushpakom S, Cedeno 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.