Study to Evaluate the Influence of Nevirapine to Atazanavir in Steady State Equilibrium in HIV Patients
Information source: Germans Trias i Pujol Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: Atazanavir (Reyataz) (Drug); Ritonavir (Norvir) (Drug); Nevirapine (Viramune) (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Germans Trias i Pujol Hospital Official(s) and/or principal investigator(s): Bonaventura Clotet, MD,PhD, Principal Investigator, Affiliation: LLuita contra la Sida Foundation-HIV Unit Jose Molto, MD,PhD, Principal Investigator, Affiliation: LLuita contra la Sida Foundation-HIV Unitat Josep Mª LLibre, MD,PhD, Principal Investigator, Affiliation: Lluita contra la Sida Foundation- HIV Unit Sílvia Valero, Principal Investigator, Affiliation: Hospital Sant Jaume de Calella
Summary
The purpose of this study is to evaluate the influence of nevirapine in exposure to
atazanavir boosted with ritonavir, in steady state equilibrium, in HIV-infected adult
patients.
Clinical Details
Official title: Clinical Pilot Trial to Evaluate the Influence of Nevirapine in Exposure to Atazanavir in Steady State Equilibrium in HIV-Infected Adult Patients.
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: The primary endpoint of the study will be the atazanavir plasma concentration
Secondary outcome: Proportion of patients with atazanavir plasma concentrations < 0.15 mg/LProportion of patients with nevirapine plasma concentrations > 6.0 mg/L Incidence of adverse events and anomalies in the laboratory tests (haemogram, AST / ALT / FA / GGT, bilirubin, creatinine, urea).
Detailed description:
In recent years, new treatment strategies have appeared aimed at reducing the risk of
treatment-derived toxicity without compromising efficacy.
Of the recent antiretroviral drugs, atazanavir is a protease inhibitor (PI) whose
pharmacokinetic profile allows it to be given in a single daily take with a scant impact on
lipid metabolism. This second characteristic makes atazanavir a good alternative for
patients with a high vascular risk. However, one of its drawbacks is that it may present
clinically relevant interactions with other drugs.
Another antiretroviral agent with a scant impact on lipid metabolism is nevirapine.
Different studies have described an improvement in lipid profile, as well as a less
atherogenic tendency in patients treated with nevirapine. Moreover, the combination of
nevirapine with PI drugs in the context of nucleoside-sparing strategies may permit a
suitable control of viral replication, and an improvement in the mitochondrial toxicity
derived from treatment with NTRI, which may possibly result in a minor incidence or in a
clinical improvement of lipodystrophy.
The combination of atazanavir with nevirapine may be of major interest in HIV-infected
patients that have had a cardiovascular event (secondary prevention) or are at a high risk
of having one (primary prevention). Similarly, this combination of drugs may be promising as
a nucleoside-sparing strategy. However, according to preliminary data, the joint
administration of nevirapine with atazanavir may lead to a reduction in the atazanavir
plasma concentration. Thus, before evaluating the clinical utility of this combination of
drugs, pharmacokinetic studies evaluating the existence of significant pharmacokinetic
interactions between both are necessary
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Age >=18 years.
- Patients infected by HIV-1 (at least one documented positive Western-Blot).
- Stable antiretroviral treatment with atazanavir boosted with ritonavir (300/100 mg
QD) for at least 14 days.
- Absence of acute infections and/or tumours in the three months prior to inclusion.
- Subject able to follow the treatment period.
- Transaminase values (AST/ALT) below 5 times the upper limit of the interval of
normality.
- In women, negative pregnancy test or not of fertile age (defined as at least one year
from menopause or undergoing any surgical sterilisation technique), or undertaking to
use a barrier contraceptive method during the study.
- Signature of the informed consent.
- Undetectable viral load.
Exclusion Criteria:
- Failure to comply with any of the inclusion criteria.
- Record of allergic hypersensitivity or intolerance to the investigational medication.
- Any clinical or historic observation that might interfere in the pharmacokinetics of
the medication, such as gastrointestinal diseases or surgery (except herniotomy or
appendectomy), alterations in the composition of plasma proteins, any indication of
hepatic or renal dysfunction.
- Patients that have been given tenofovir, omeprazole or other proton pump inhibitors
or any other medication with relevant interactions with atazanavir within the two
weeks prior to the screening visit.
- Active consumption of alcohol (> 50 g/day) or illegal drugs (except cannabis).
- Suspicion of unsuitable antiretroviral treatment compliance.
- Pregnancy or breastfeeding.
Locations and Contacts
Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona 08916, Spain
Hospital Sant Jaume de Calella, Calella, Barcelona 08370, Spain
Additional Information
Starting date: January 2007
Last updated: June 16, 2009
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