Study to Evaluate the Influence of Nevirapine to Atazanavir in Steady State Equilibrium in HIV Patients - Full Text View

Sponsors and Collaborators:	Germans Trias i Pujol Hospital FUNDACIÓ LLUITA CONTRA LA SIDA Hospital San Jaime de Calella
Information provided by:	Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier:	NCT00355719

Purpose

To evaluate the influence of nevirapine in exposure to atazanavir boosted with ritonavir, in steady state equilibrium, in HIV-infected adult patients.

Condition	Intervention	Phase
HIV Infections	Drug: Atazanavir (Reyataz) Drug: Ritonavir (Norvir) Drug: Nevirapine (Viramune)	Phase IV

MedlinePlus related topics: AIDS

Drug Information available for: Ritonavir Nevirapine Atazanavir sulfate BMS 232632

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety Study
Official Title:	Clinical Pilot Trial to Evaluate the Influence of Nevirapine in Exposure to Atazanavir in Steady State Equilibrium in HIV-Infected Adult Patients.

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

Primary Outcome Measures:

The primary endpoint of the study will be the atazanavir plasma concentration [ Time Frame: at baseline and week 4 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Proportion of patients with atazanavir plasma concentrations < 0.15 mg/L [ Time Frame: at baseline and week 4 ] [ Designated as safety issue: No ]
Proportion of patients with atazanavir plasma concentrations > 3.4 mg/L [ Time Frame: at baseline and week 4 ] [ Designated as safety issue: No ]
Incidence of adverse events and anomalies in the laboratory tests (haemogram, AST / ALT / FA / GGT, bilirubin, creatinine, urea). [ Time Frame: during the 8 weeks of follow-up ] [ Designated as safety issue: Yes ]

Enrollment:	14
Study Start Date:	January 2007
Study Completion Date:	February 2008
Primary Completion Date:	January 2007 (Final data collection date for primary outcome measure)

Intervention Details:

Atazanavir (Reyataz): capsules 150 mg (2 capsules/24h)

Ritonavir (Norvir): capsules 100 mg (1 capsule/24h)

Nevirapine (Viramune): tablets 200 mg (1 tablet/12h*)

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

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00355719

Locations

Spain, Barcelona
Hospital Sant Jaume de Calella
Calella, Barcelona, Spain, 08370
Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, Spain, 08916

Sponsors and Collaborators

Germans Trias i Pujol Hospital

FUNDACIÓ LLUITA CONTRA LA SIDA

Hospital San Jaime de Calella

Investigators

Principal Investigator:	Bonaventura Clotet, MD,PhD	LLuita contra la Sida Foundation-HIV Unit
Principal Investigator:	Jose Molto, MD,PhD	LLuita contra la Sida Foundation-HIV Unitat
Principal Investigator:	Josep Mª LLibre, MD,PhD	Lluita contra la Sida Foundation- HIV Unit
Principal Investigator:	Sílvia Valero	Hospital Sant Jaume de Calella

More Information

Responsible Party:	LLuita Sida Foundation ( LLuita Sida Foundation )
Study ID Numbers:	NEVIATAZ, 2006-001140-31
Study First Received:	July 24, 2006
Last Updated:	May 6, 2008
ClinicalTrials.gov Identifier:	NCT00355719
Health Authority:	Spain: Ministry of Health

Keywords provided by Germans Trias i Pujol Hospital:

Nevirapine
Atazanavir
Pharmacokinetics
Interactions

Study placed in the following topic categories:

Virus Diseases
Nevirapine
Sexually Transmitted Diseases, Viral
Ritonavir
HIV Infections

Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Atazanavir
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:

Anti-Infective Agents
HIV Protease Inhibitors
RNA Virus Infections
Slow Virus Diseases
Anti-HIV Agents
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Enzyme Inhibitors
Infection

Antiviral Agents
Pharmacologic Actions
Protease Inhibitors
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 14, 2009